Advances in the structural characterization of complexes of therapeutic antibodies with PD-1 or PD-L1

References

• Postow MA, Callahan MK, Wolchok JD. Immune checkpoint blockade in cancer therapy. J Clin Onco. 2015;33:1974–17. doi:10.1200/jco.2014.59.4358. PMID: WOS:000355999800019.
   PubMed Web of Science ®Google Scholar
• Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018;359:1350–55. doi:10.1126/science.aar4060. PMID: WOS:000428043600036.
   PubMed Web of Science ®Google Scholar
• Sharma P, Allison JP. The future of immune checkpoint therapy. Science. 2015;348:56–61. doi:10.1126/science.aaa8172. PMID: WOS:000352079500026.
   PubMed Web of Science ®Google Scholar
• Okazaki T, Honjo T. PD-1 and PD-1 ligands: from discovery to clinical application. Int Immunol. 2007;19:813–24. doi:10.1093/intimm/dxm057. PMID: WOS:000249127900001.
   PubMed Web of Science ®Google Scholar
• Callahan MK, Postow MA, Wolchok JD. Targeting T cell co-receptors for cancer therapy. Immun. 2016;44:1069–78. doi:10.1016/j.immuni.2016.04.023. PMID: WOS:000376478500008.
   Google Scholar
• Tan S, Chen D, Liu K, He M, Song H, Shi Y, Liu J, Zhang CWH, Qi J, Yan J, et al. Crystal clear: visualizing the intervention mechanism of the PD-1/PD-L1 interaction by two cancer therapeutic monoclonal antibodies. Protein Cell. 2016;7(12):866–77. doi:10.1007/s13238-016-0337-7. PMID: WOS:000391431600004.
   PubMed Web of Science ®Google Scholar
• Wherry EJ. T cell exhaustion. Nat Immunol. 2011;12:492–99. doi:10.1038/ni.2035. PMID: WOS:000290707100007.
   PubMed Web of Science ®Google Scholar
• Dong HD, Zhu GF, Tamada K, Chen LP. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med. 1999;5:1365–69. doi:10.1038/70932. WOS:000084049700034. PMID: WOS:000084049700034.
   PubMed Web of Science ®Google Scholar
• Ahmadzadeh M, Johnson LA, Heemskerk B, Wunderlich JR, Dudley ME, White DE, Rosenberg SA. Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood. 2009;114:1537–44. doi:10.1182/blood-2008-12-195792. PMID: WOS:000269380300015.
   PubMed Web of Science ®Google Scholar
• Hawkes EA, Grigg A, Chong G. Programmed cell death-1 inhibition in lymphoma. Lancet Oncol. 2015;16:E234–E45. doi:10.1016/s1470-2045(15)70103-8. PMID: WOS:000353908200025.
   PubMed Web of Science ®Google Scholar
• Chen L, Han X. Anti–PD-1/PD-L1 therapy of human cancer: past, present, and future. J Clin Investigat. 2015;125(9):3384–91. PMID: WOS:000362303600013. doi:10.1172/jci80011.
   PubMed Web of Science ®Google Scholar
• Okazaki T, Honjo T. The PD-1–PD-L pathway in immunological tolerance. Trends Immunol. 2006;27(4):195–201. PMID: WOS:000237145700008. doi:10.1016/j.it.2006.02.001.
   PubMed Web of Science ®Google Scholar
• Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, McDermott DF, Powderly JD, Gettinger SN, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014;515:563–67. doi:10.1038/nature14011. PMID: WOS:000346247600053.
   PubMed Web of Science ®Google Scholar
• Schumacher TN, Kesmir C, van Buuren MM. Biomarkers in cancer immunotherapy. Cancer Cell. 2015;27:12–14. doi:10.1016/j.ccell.2014.12.004. PMID: WOS:000347906900006.
   PubMed Web of Science ®Google Scholar
• Hoy SM. Sintilimab: first global approval. Drugs. 2019;79:341–46. doi:10.1007/s40265-019-1066-z. PMID: WOS:000459785400010.
   PubMed Web of Science ®Google Scholar
• Keam SJ. Toripalimab: first global approval. Drugs. 2019;79:573–78. doi:10.1007/s40265-019-01076-2. PMID: WOS:000463813000009.
   PubMed Web of Science ®Google Scholar
• Lee A. Serplulimab: first approval. Drugs. 2022;82:1137–41. doi:10.1007/s40265-022-01740-0. PMID: WOS:000825375200001.
   PubMed Web of Science ®Google Scholar
• Lee AN, Keam SJ. Tislelizumab: first approval. Drugs. 2020;80:617–24. doi:10.1007/s40265-020-01286-z. PMID: WOS:000520675700002.
   PubMed Web of Science ®Google Scholar
• Markham A. Zimberelimab: first approval. Drugs. 2021;81:2063–68. doi:10.1007/s40265-021-01628-5. PMID: WOS:000712334300001.
   PubMedGoogle Scholar
• Markham A, Duggan S. Cemiplimab: first global approval. Drugs. 2018;78(17):1841–46. PMID: WOS:000451587400008. doi:10.1007/s40265-018-1012-5.
   PubMed Web of Science ®Google Scholar
• Markham A, Keam SJ. Camrelizumab: first global approval. Drugs. 2019;79(12):1355–61. PMID: WOS:000479057000008. doi:10.1007/s40265-019-01167-0.
   PubMed Web of Science ®Google Scholar
• Paik J. Nivolumab plus relatlimab: first approval. Drugs. 2022;82(8):925–31. PMID: WOS:000793714400001. doi:10.1007/s40265-022-01723-1.
   PubMed Web of Science ®Google Scholar
• Poole RM. Pembrolizumab: first global approval. Drugs. 2014;74(16):1973–81. PMID: WOS:000344619000008. doi:10.1007/s40265-014-0314-5.
   PubMed Web of Science ®Google Scholar
• Dhillon S. Penpulimab: first approval. Drugs. 2021;81(18):2159–66. PMID: WOS:000721652600001. doi:10.1007/s40265-021-01640-9.
   PubMed Web of Science ®Google Scholar
• Markham A. Dostarlimab: first approval. Drugs. 2021;81(10):1213–19. PMID: WOS:000659390700002. doi:10.1007/s40265-021-01539-5.
   PubMed Web of Science ®Google Scholar
• Syed YY. Durvalumab: first global approval. Drugs. 2017;77(12):1369–76. PMID: WOS:000406276900009. doi:10.1007/s40265-017-0782-5.
   PubMed Web of Science ®Google Scholar
• Rao A, Patel MR. A review of avelumab in locally advanced and metastatic bladder cancer. Ther Adv Urol. 2019;11:1756287218823485. doi:10.1177/1756287218823485. PMID: WOS:000457393900001.
   Web of Science ®Google Scholar
• Markham A. Envafolimab: first approval. Drugs. 2022;82(2):235–40. PMID: WOS:000751583100001. doi:10.1007/s40265-022-01671-w.
   PubMed Web of Science ®Google Scholar
• Markham A. Atezolizumab: first global approval. Drugs. 2016;76(12):1227–32. PMID: WOS:000380745400007. doi:10.1007/s40265-016-0618-8.
   PubMed Web of Science ®Google Scholar
• Zak KM, Kitel R, Przetocka S, Golik P, Guzik K, Musielak B, Domling A, Dubin G, Holak TA. Structure of the complex of human programmed death 1, PD-1, and its ligand PD-L1. Struct. 2015;23:2341–48. doi:10.1016/j.str.2015.09.010. PMID: WOS:000366171500016.
   Google Scholar
• Pascolutti R, Sun XQ, Kao J, Maute RL, Ring AM, Bowman GR, Kruse AC. Structure and dynamics of PD-L1 and an ultra-high-affinity PD-1 receptor mutant. Struct. 2016;24:1719–28. doi:10.1016/j.str.2016.06.026. PMID: WOS:000386763800011.
   Google Scholar
• Lin DW, Tanaka Y, Iwasaki M, Gittis AG, Su HP, Mikami B, Okazaki T, Honjo T, Minato N, Garboczi DN. The PD-1/PD-L1 complex resembles the antigen-binding Fv domains of antibodies and T cell receptors. P Natl Acad Sci Usa. 2008;105:3011–16. doi:10.1073/pnas.0712278105. PMID: WOS:000253567900048.
   PubMed Web of Science ®Google Scholar
• Horita S, Nomura Y, Sato Y, Shimamura T, Iwata S, Nomura N. High-resolution crystal structure of the therapeutic antibody pembrolizumab bound to the human PD-1. Sci Rep-Uk. 2016;6(1):35297. PMID: WOS:000385346100001. doi:10.1038/srep35297.
   PubMedGoogle Scholar
• Na Z, Yeo SP, Bharath SR, Bowler MW, Balikci E, Wang CI, Song H. Structural basis for blocking PD-1-mediated immune suppression by therapeutic antibody pembrolizumab. Cancer Res. 2017;27:147–50. doi:10.1038/cr.2016.77. PMID: WOS:000392277900014.
   Google Scholar
• Lee JY, Lee HT, Shin W, Chae J, Choi J, Kim SH, Lim H, Heo TW, Park KY, Ryu SE, et al. Structural basis of checkpoint blockade by monoclonal antibodies in cancer immunotherapy. Nat Commun. 2016;7. doi:10.1038/ncomms13354. PMID: WOS:000386515200001.
   Web of Science ®Google Scholar
• Tan S, Zhang H, Chai Y, Song H, Tong Z, Wang Q, Qi J, Wong G, Zhu X, Liu WJ, et al. An unexpected N-terminal loop in PD-1 dominates binding by nivolumab. Nat Commun. 2017;8(1):14369. doi:10.1038/ncomms14369. PMID: WOS:000393375400001.
   PubMed Web of Science ®Google Scholar
• Lu D, Xu Z, Zhang D, Jiang M, Liu K, He J, Ma D, Ma X, Tan S, Gao GF, et al. PD-1 N58-glycosylation-dependent binding of monoclonal antibody cemiplimab for immune checkpoint therapy. Front Immunol. 2022;13:826045. doi:10.3389/fimmu.2022.826045. PMID: WOS:000771576300001.
   PubMed Web of Science ®Google Scholar
• Sang HL, Lee HT, Lim H, Kim Y, Heo YSJB, Communications BR. Crystal structure of PD-1 in complex with an antibody-drug tislelizumab used in tumor immune checkpoint therapy. Biochem Bioph Res Co. 2020;527(1):226–31. doi:10.1016/j.bbrc.2020.04.121.
   PubMed Web of Science ®Google Scholar
• Hong Y, Feng Y, Sun H, Zhang B, Wu H, Zhu Q, Li Y, Zhang T, Zhang Y, Cui X, et al. Tislelizumab uniquely binds to the CC′ loop of PD-1 with slow-dissociated rate and complete PD-L1 blockage. FEBS Open Bio. 2021;11(3):782–92. doi:10.1002/2211-5463.13102. PMID: WOS:000618375800001.
   PubMed Web of Science ®Google Scholar
• Liu K, Tan S, Jin W, Guan J, Wang Q, Sun H, Qi J, Yan J, Chai Y, Wang Z, et al. N-glycosylation of PD-1 promotes binding of camrelizumab. EMBO Rep. 2020;21(12):e51444. doi:10.15252/embr.202051444. PMID: WOS:000577337200001.
   PubMed Web of Science ®Google Scholar
• Liu H, Guo L, Zhang J, Zhou Y, Zhou J, Yao J, Wu H, Yao S, Chen B, Chai Y, et al. Glycosylation-independent binding of monoclonal antibody toripalimab to FG loop of PD-1 for tumor immune checkpoint therapy. MAbs. 2019;11(4):681–90. doi:10.1080/19420862.2019.1596513. PMID: WOS:000476960300006.
   PubMed Web of Science ®Google Scholar
• Issafras H, Fan S, Tseng CL, Cheng Y, Lin P, Xiao L, Huang YJ, Tu CH, Hsiao YC, Li M, et al. Structural basis of HLX10 PD-1 receptor recognition, a promising anti-PD-1 antibody clinical candidate for cancer immunotherapy. PLoS One. 2021;16(12):e0257972. doi:10.1371/journal.pone.0257972. PMID: WOS:000773555700007.
   PubMed Web of Science ®Google Scholar
• Zhang F, Qi X, Wang X, Wei D, Wu J, Feng L, Cai H, Wang Y, Zeng N, Xu T, et al. Structural basis of the therapeutic anti-PD-L1 antibody atezolizumab. Oncotarget. 2017;8:90215–24. doi:10.18632/oncotarget.21652. PMID: WOS:000414097100066.
   PubMedGoogle Scholar
• Lee HT, Lee JY, Lim H, Lee SH, Moon YJ, Pyo HJ, Ryu SE, Shin W, Heo YS. Molecular mechanism of PD-1/PD-L1 blockade via anti-PD-L1 antibodies atezolizumab and durvalumab. Sci Rep-Uk. 2017;7:5532. doi:10.1038/s41598-017-06002-8. PMID: WOS:000405675400012.
   PubMed Web of Science ®Google Scholar
• Tan S, Liu K, Chai Y, Zhang CWH, Gao S, Gao GF, Qi J. Distinct PD-L1 binding characteristics of therapeutic monoclonal antibody durvalumab. Protein Cell. 2018;9(1):135–39. PMID: WOS:000423135400011. doi:10.1007/s13238-017-0412-8.
   PubMed Web of Science ®Google Scholar
• Liu K, Tan S, Chai Y, Chen D, Song H, Zhang CH, Shi Y, Liu J, Tan W, Lyu J, et al. Structural basis of anti-PD-L1 monoclonal antibody avelumab for tumor therapy. Cancer Res. 2017;27:151–53. doi:10.1038/cr.2016.102. PMID: WOS:000392277900015.
   Google Scholar
• Zhang F, Wei H, Wang X, Bai Y, Wang P, Wu J, Jiang X, Wang Y, Cai H, Xu T, et al. Structural basis of a novel PD-L1 nanobody for immune checkpoint blockade. Cell Discov. 2017;3(1):17004. doi:10.1038/celldisc.2017.4. PMID: WOS:000414903600001.
   PubMedGoogle Scholar
• Lazar-Molnar E, Yan QR, Cao E, Ramagopal U, Nathenson SG, Almo SC. Crystal structure of the complex between programmed death-1 (PD-1) and its ligand PD-L2. Proc Natl Acad Sci USA. 2008;105(30):10483–88. PMID: WOS:000258211600039. doi:10.1073/pnas.0804453105.
   PubMed Web of Science ®Google Scholar
• Cheng XX, Veverka V, Radhakrishnan A, Waters LC, Muskett FW, Morgan SH, Huo JD, Yu C, Evans EJ, Leslie AJ, et al. Structure and interactions of the human programmed cell death 1 receptor. J Biol Chem. 2013;288(17):11771–85. doi:10.1074/jbc.M112.448126. PMID: WOS:000318157600014.
   PubMed Web of Science ®Google Scholar
• Tan SG, Zhang CWH, Gao GF. Seeing is believing: anti-PD-1/PD-L1 monoclonal antibodies in action for checkpoint blockade tumor immunotherapy. Signal Transduct Tar. 2016;1(1):e16029. PMID: WOS:000454602900017. doi:10.1038/sigtrans.2016.29.
   PubMedGoogle Scholar
• Tan SG, Chen DQ, Liu KF, He MN, Song H, Shi Y, Liu J, Zhang C, Qi JX, Yan JH, et al. Crystal clear: visualizing the intervention mechanism of the PD-1/PD-L1 interaction by two cancer therapeutic monoclonal antibodies. Protein Cell. 2016;7(12):866–77. doi:10.1007/s13238-016-0337-7. PMID: WOS:000391431600004.
   PubMed Web of Science ®Google Scholar
• Shin J, Phelan PJ, Gjoerup O, Bachovchin W, Bullock PA. Characterization of a single chain variable fragment of nivolumab that targets PD-1 and blocks PD-L1 binding. Protein Expres Purif. 2021;177:105766. doi:10.1016/j.pep.2020.105766. PMID: WOS:000579451300016.
   PubMed Web of Science ®Google Scholar
• Sahu M, Zimberelimab CJ. Anti-programmed cell death protein 1 (PD-1) monoclonal antibody, Treatment of hodgkin lymphoma, treatment of advanced solid tumors. Drugs Fut. 2022;47(2):115–21. PMID: WOS:000759046000001. doi:10.1358/dof.2022.47.2.3400575.
   Google Scholar
• Mittal L, Srivastava M, Kumari A, Tonk RK, Awasthi A, Asthana S. Interplay among structural stability, plasticity, and energetics determined by conformational attuning of flexible loops in PD-1. J Chem Inf Model. 2021;61(1):358–84. PMID: WOS:000613719400033. doi:10.1021/acs.jcim.0c01080.
   PubMed Web of Science ®Google Scholar
• Lu D, Xu ZP, Zhang D, Jiang M, Liu KF, He JH, Ma DL, Ma XP, Tan SG, Gao GF, et al. PD-1 N58-gycosylation-dependent binding of monoclonal antibody cemiplimab for immune checkpoint therapy. Front Immunol. 2022;13:826045. doi:10.3389/fimmu.2022.826045. PMID: WOS:000771576300001.
   PubMed Web of Science ®Google Scholar
• Liu KF, Tan SG, Jin WJ, Guan JW, Wang QL, Sun H, Qi JX, Yan JH, Chai Y, Wang ZF, et al. N-glycosylation of PD-1 promotes binding of camrelizumab. EMBO Rep. 2020;21(12):e51444. doi:10.15252/embr.202051444. PMID: WOS:000577337200001.
   PubMed Web of Science ®Google Scholar
• Liu HC, Guo LJ, Zhang J, Zhou YH, Zhou JW, Yao J, Wu H, Yao S, Chen B, Chai Y, et al. Glycosylation-independent binding of monoclonal antibody toripalimab to FG loop of PD-1 for tumor immune checkpoint therapy. MAbs. 2019;11(4):681–90. doi:10.1080/19420862.2019.1596513. PMID: WOS:000476960300006.
   PubMed Web of Science ®Google Scholar
• Lee HT, Lee SH, Heo YS. Molecular interactions of antibody drugs targeting PD-1, PD-L1, and CTLA-4 in immuno-oncology. Molecules. 2019;24:1190. doi:10.3390/molecules24061190. PMID: WOS:000465503800152.
   PubMed Web of Science ®Google Scholar
• Issafras H, Fan SL, Tseng CL, Cheng YC, Lin PH, Xiao LS, Huang YJ, Tu CH, Hsiao YC, Li M, et al. Structural basis of HLX10 PD-1 receptor recognition, a promising anti-PD-1 antibody clinical candidate for cancer immunotherapy. PLoS One. 2021;16(12):e0257972. doi:10.1371/journal.pone.0257972. PMID: WOS:000773555700007.
   PubMed Web of Science ®Google Scholar
• Ferris RL, Blumenschein G Jr., Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375(19):1856–67. doi:10.1056/NEJMoa1602252. PMID: WOS:000387534200009.
   PubMed Web of Science ®Google Scholar
• Feng YC, Hong Y, Sun HZ, Zhang B, Wu HF, Li K, Liu XS, Liu Y. The molecular binding mechanism of tislelizumab, an investigational anti-PD-1 antibody, is differentiated from pembrolizumab and nivolumab. Cancer Res. 2019;79(13_Supplement):2383–2383. PMID: WOS:000488279400352. doi:10.1158/1538-7445.Am2019-2383.
   Web of Science ®Google Scholar
• Zhang F, Wei HD, Wang XX, Bai Y, Wang PL, Wu JW, Jiang XY, Wang YG, Cai HY, Xu T, et al. Structural basis of a novel PD-L1 nanobody for immune checkpoint blockade. Cell Discov. 2017;3(1):17004. doi:10.1038/celldisc.2017.4. PMID: WOS:000414903600001.
   PubMedGoogle Scholar
• Tan SG, Liu KF, Chai Y, Zhang CWH, Gao S, Gao G, Qi JX. Distinct PD-L1 binding characteristics of therapeutic monoclonal antibody durvalumab. Protein Cell. 2018;9(1):135–39. PMID: WOS:000423135400011. doi:10.1007/s13238-017-0412-8.
   PubMed Web of Science ®Google Scholar
• Liu KF, Tan SG, Chai Y, Chen DQ, Song H, Zhang CWH, Shi Y, Liu J, Tan WJ, Lyu JX, et al. Structural basis of anti-PD-L1 monoclonal antibody avelumab for tumor therapy. Cancer Res. 2017;27(1):151–53. doi:10.1038/cr.2016.102. PMID: WOS:000392277900015.
   Google Scholar
• Cordova-Bahena L, Velasco-Velazquez MA. Anti-PD-1 and anti-PD-L1 antibodies as imminotherapy against cancer: a structural perspective. Rev Invest Clin. 2021;73:8–16. doi:10.24875/ric.20000341. PMID: WOS:000662706100003.
   Google Scholar
• Makaremi S, Asadzadeh Z, Hemmat N, Baghbanzadeh A, Sgambato A, Ghorbaninezhad F, Safarpour H, Argentiero A, Brunetti O, Bernardini R, et al. Immune checkpoint inhibitors in colorectal cancer: challenges and future prospects. Biomed. 2021;9(9):1075. doi:10.3390/biomedicines9091075. PMID: WOS:000699157400001.
   Google Scholar
• Lin X, Lu X, Luo GS, Xiang H. Progress in PD-1/PD-L1 pathway inhibitors: from biomacromolecules to small molecules. Eur J Med Chem. 2020;186:111876. doi:10.1016/j.ejmech.2019.111876. PMID: WOS:000509616800004.
   PubMed Web of Science ®Google Scholar
• Mittal L, Tonk R, Awasthi A, Asthana S. Traversing through the dynamic protein–protein interaction landscape and conformational plasticity of PD-1 for small-molecule discovery. J Med Chem. 2022;65(8):5941–53. PMID: WOS:000797573100006. doi:10.1021/acs.jmedchem.2c00176.
   PubMed Web of Science ®Google Scholar
• Park UB, Jeong TJ, Gu N, Lee HT, Heo YS. Molecular basis of PD-1 blockade by dostarlimab, the FDA-approved antibody for cancer immunotherapy. Biochem Bioph Res Co. 2022;599:31–37. doi:10.1016/j.bbrc.2022.02.026. PMID: WOS:000755175000005.
   PubMed Web of Science ®Google Scholar
• Tang SG, Kim PS. A high-affinity human PD-1/PD-L2 complex informs avenues for small-molecule immune checkpoint drug discovery. P Natl Acad Sci Usa. 2019;116:24500–06. doi:10.1073/pnas.1916916116. PMID: WOS:000500804600026.
   PubMed Web of Science ®Google Scholar
• Lee SH, Lee HT, Lim H, Kim Y, Park UB, Heo YS. Crystal structure of PD-1 in complex with an antibody-drug tislelizumab used in tumor immune checkpoint therapy. Biochem Bioph Res Co. 2020;527:226–31. doi:10.1016/j.bbrc.2020.04.121. PMID: WOS:000535964300034.
   PubMed Web of Science ®Google Scholar
• Vidarsson G, Dekkers G, Rispens T. IgG subclasses and allotypes: from structure to effector functions. Front Immunol. 2014;5:520. doi:10.3389/fimmu.2014.00520. PMID: WOS:000354496200001.
   PubMed Web of Science ®Google Scholar
• Kim DW, Zager JS, Eroglu Z. Improving clinical outcomes with pembrolizumab in patients with advanced melanoma. Chin Clin Oncol. 2017;6:2–2. doi:10.21037/cco.2017.01.04. PMID: MEDLINE:28285535.
   PubMedGoogle Scholar
• Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, Gottfried M, Peled N, Tafreshi A, Cuffe S, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. New Engl J Med. 2016;375:1823–33. doi:10.1056/NEJMoa1606774. PMID: WOS:000387534200006.
   PubMed Web of Science ®Google Scholar
• Burtness B, Harrington KJ, Greil R. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study (vol 394, pg 1915, 2019). Lancet. 2020;395:564–564. WOS:000514849400026. PMID: WOS:000514849400026.
   Google Scholar
• Riano I, Patel SR, Liu SV, Duma N. Evidence to date: evaluating pembrolizumab in the treatment of extensive-stage small-cell lung cancer. Clinics Pract. 2021;11:441–54. doi:10.3390/clinpract11030059. PMID: MEDLINE:34287275.
   PubMed Web of Science ®Google Scholar
• Lyu MM, Shen Y, Beharee N, Lu J, Deng F, Wang JH. The combined use of chemotherapy and radiotherapy with PD- I inhibitor, pembrolizumab, in advanced cervical cancer: a case report. OncoTargets Ther. 2020;13:4465–71. doi:10.2147/ott.S245190. PMID: WOS:000534220600001.
   PubMed Web of Science ®Google Scholar
• Asmar R, Yang J, Carvajal RD. Clinical utility of nivolumab in the treatment of advanced melanoma. Ther Clin Risk Manag. 2016;12:313–25. doi:10.2147/tcrm.S78039. PMID: WOS:000370939200001.
   PubMed Web of Science ®Google Scholar
• Cortinovis DL, Canova S, Abbate M, Colonese F, Bidoli P. Focus on nivolumab in NSCLC. Front Med-Lausanne. 2016;3:67. doi:10.3389/fmed.2016.00067. PMID: WOS:000407067900001.
   PubMed Web of Science ®Google Scholar
• Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, Schuster SJ, Millenson MM, Cattry D, Freeman GJ, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. New Engl J Med. 2015;372:311–19. doi:10.1056/NEJMoa1411087. PMID: WOS:000348204500006.
   PubMed Web of Science ®Google Scholar
• Song Y, Gao Q, Zhang H, Fan L, Zhou J, Zou D, Li W, Yang H, Liu T, Wang Q, et al. Tislelizumab (BGB-A317) for relapsed/refractory classical Hodgkin lymphoma: preliminary efficacy and safety results from a phase 2 study. Blood. 2018;132(Supplement 1):682–682. doi:10.1182/blood-2018-99-117848. PMID: WOS:000454837602060.
   Google Scholar
• Ye D, Liu J, Zhou A, Zou Q, Li H, Fu C, Hu H, Huang J, Zhu S, Jin J, et al. Tislelizumab in Asian patients with previously treated locally advanced or metastatic urothelial carcinoma. Cancer Sci. 2021;112:305–13. doi:10.1111/cas.14681. PMID: WOS:000585909300001.
   PubMed Web of Science ®Google Scholar
• Liu SY, Wu YL. Tislelizumab: an investigational anti-PD-1 antibody for the treatment of advanced non-small cell lung cancer (NSCLC). Expert Opin Inv Drug. 2020;29(12):1355–63. doi:10.1080/13543784.2020.1833857. PMID:WOS:000580619700001.
   PubMed Web of Science ®Google Scholar
• Kudo M. Systemic therapy for hepatocellular carcinoma: latest advances. Cancers. 2018;10:412. doi:10.3390/cancers10110412. PMID: WOS:000451307700019.
   PubMed Web of Science ®Google Scholar
• Song YQ, Wu JQ, Chen XC, Lin TY, Cao JN, Liu YY, Zhao YZ, Jin J, Huang HW, Hu JD, et al. A single-arm, multicenter, phase II study of camrelizumab in relapsed or refractory classical Hodgkin lymphoma. Clin Cancer Res. 2019;25:7363–69. doi:10.1158/1078-0432.Ccr-19-1680. PMID: WOS:000509983400013.
   PubMed Web of Science ®Google Scholar
• Qin SK, Ren ZG, Meng ZQ, Chen ZD, Chai XL, Xiong JP, Bai YX, Yang L, Zhu H, Fang WJ, et al. Camrelizumab in patients with previously treated advanced hepatocellular carcinoma: a multicentre, open-label, parallel-group, randomised, phase 2 trial. Lancet Oncol. 2020;21:571–80. doi:10.1016/s1470-2045(20)30011-5. PMID: WOS:000522625000033.
   PubMed Web of Science ®Google Scholar
• Huang J, Xu JM, Chen Y, Zhuang W, Zhang YP, Chen ZD, Chen J, Zhang HL, Niu ZX, Fan QX, Lin, L., et al. Camrelizumab versus investigator’s choice of chemotherapy as second-line therapy for advanced or metastatic oesophageal squamous cell carcinoma (ESCORT): a multicentre, randomised, open-label, phase 3 study. Lancet Oncol. 2020;21(6):832–42. doi:10.1016/s1470-2045(20)30110-8. PMID: WOS:000544057400034.
   PubMed Web of Science ®Google Scholar
• Fang WF, Yang YP, Ma YX, Hong SD, Lin LZ, He XH, Xiong JP, Li P, Zhao HY, Huang Y, et al. Camrelizumab (SHR-1210) alone or in combination with gemcitabine plus cisplatin for nasopharyngeal carcinoma: results from two single-arm, phase 1 trials. Lancet Oncol. 2018;19:1338–50. doi:10.1016/s1470-2045(18)30495-9. PMID: WOS:000446052800054.
   PubMed Web of Science ®Google Scholar
• Sun GG, Jia JH, Gao P, Yao XM, Chen MD, Yao WN, Sun L, Wang W. Activity and safety of camrelizumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced non-small-cell lung cancer. J ImmunoTher Cancer. 2020;8:A267–A68. doi:10.1136/jitc-2020-SITC2020.0440. PMID: WOS:000616665300428.
   Google Scholar
• Tang BX, Chi ZH, Guo J. Toripalimab for the treatment of melanoma. Expert Opin Biol Th. 2020;20:863–69. doi:10.1080/14712598.2020.1762561. PMID: WOS:000534142800001.
   PubMed Web of Science ®Google Scholar
• Wang FH, Wei XL, Feng JF, Li Q, Xu N, Hu XC, Liao WJ, Jiang Y, Lin XY, Zhang QY, et al. Efficacy, safety, and correlative biomarkers of toripalimab in previously treated recurrent or metastatic nasopharyngeal carcinoma: a phase II clinical trial (POLARIS-02). J Clin Onco. 2021;39:704–12. doi:10.1200/jco.20.02712. PMID: WOS:000635371200003.
   PubMed Web of Science ®Google Scholar
• Zan N, Zhang X, Du LY, Lin ZY, Yu DF, Liu J, Gou FS. Case report: toripalimab combined with anlotinib in a patient with metastatic upper tract urothelial carcinoma after pembrolizumab failure. Front Oncol. 2022;12(796407):796407. doi:10.3389/fonc.2022.796407. PMID: WOS:000770970400001.
   PubMedGoogle Scholar
• Poh A. Assessing toripalimab in NSCLC. Cancer Discov. 2022;12:1176–77. doi:10.1158/2159-8290.Cd-nb2022-0022. PMID: WOS:000795608300005.
   Web of Science ®Google Scholar
• Ghidini A, Santangelo D, Vaccaro G, Chillura M, Petrelli F. Cemiplimab in cutaneous squamous cell carcinomas (SCC): an overview and a clinical case. Oral Oncol. 2022;128:105847. doi:10.1016/j.oraloncology.2022.105847. PMID: WOS:000792738900003.
   PubMed Web of Science ®Google Scholar
• Naik PP. Cemiplimab in advanced cutaneous squamous cell carcinoma. Dermatol Ther. 2021;34:e15184. doi:10.1111/dth.15184. PMID: WOS:000715489200001.
   PubMed Web of Science ®Google Scholar
• Ren Z, Shao G, Shen J, Zhang L, Zhu X, Fang W, Sun G, Bai Y, Wu J, Liu L, et al. Phase 2 study of the PD-1 inhibitor serplulimab plus the bevacizumab biosimilar HLX04 in patients with previously treated advanced hepatocellular carcinoma. Liver Cancer. 2022;12(2):116–28. doi:10.1159/000526638. PMID: WOS:000848468700001.
   PubMed Web of Science ®Google Scholar
• Oaknin A, Tinker AV, Gilbert L, Samouelian V, Mathews C, Brown J, Barretina-Ginesta MP, Moreno V, Gravina A, Abdeddaim C, et al. Clinical activity and safety of the anti-PD-1 monoclonal antibody dostarlimab for patients with recurrent or advanced dMMR endometrial cancer. Future Oncol. 2021;17:3781–85. doi:10.2217/fon-2021-0598. PMID: WOS:000687857400001.
   PubMed Web of Science ®Google Scholar
• Liu XH, Yi Y. Sintilimab plus sorafenib: a novel regimen for hepatocellular carcinoma. Immunotherapy-Uk. 2021;13:1387–93. doi:10.2217/imt-2021-0062. PMID: WOS:000708528700001.
   PubMed Web of Science ®Google Scholar
• Lv HL, Tian Y, Li JC, Huang C, Sun BK, Gai CY, Li ZH, Tian ZQ. Neoadjuvant sintilimab plus chemotherapy in resectable locally advanced esophageal squamous cell carcinoma. Front Oncol. 2022;12:864533. doi:10.3389/fonc.2022.864533. PMID: WOS:000795234900001.
   PubMedGoogle Scholar
• Zhang L, Lin WH, Tan FW, Li N, Xue Q, Gao SG, Gao YB, He J. Sintilimab for the treatment of non-small cell lung cancer. Biomark Res. 2022;10:23. doi:10.1186/s40364-022-00363-7. PMID: WOS:000786459400001.
   PubMed Web of Science ®Google Scholar
• Deng M. The approval of sintilimab for classical Hodgkin’s lymphoma: views and perspectives of anti-PD-1/PD-L1 antibodies in China. Antib Ther. 2019;2:54–55. doi:10.1093/abt/tbz005. PMID: MEDLINE:33928222.
   PubMedGoogle Scholar
• Haddley K. Dostarlimab anti-PD-1 monoclonal antibody treatment of advanced solid tumors. Drug Future. 2019;44:527–34. doi:10.1358/dof.2019.044.07.3023389. PMID: WOS:000478690100002.
   Web of Science ®Google Scholar
• Song Y, Zhou K, Jin C, Qian Z, Hou M, Fan L, Li F, Ding K, Zhou H, Li X, et al. A phase II study of penpulimab, an anti-PD-1 antibody, in patients with relapsed or refractoryclassic Hodgkin lymphoma (cHL). J Clin Onco. 2021;39(15_suppl):7529–7529. doi:10.1200/JCO.2021.39.15_suppl.7529. PMID: WOS:000708120604126.
   Google Scholar
• Lin NJ, Zhang MZ, Bai H, Liu H, Cui J, Ke XY, Zhang HL, Liu LH, Yan DM, Jiang YS, et al. Efficacy and safety of GLS-010 (zimberelimab) in patients with relapsed or refractory classical Hodgkin lymphoma: A multicenter, single-arm, phase II study. Eur J Cancer. 2022;164:117–26. doi:10.1016/j.ejca.2021.07.021. PMID: WOS:000792600200013.
   PubMed Web of Science ®Google Scholar
• Crist M, Balar A. Atezolizumab in invasive and metastatic urothelial carcinoma. Expert Rev Clin Phar. 2017;10:1295–301. doi:10.1080/17512433.2017.1389275. PMID: WOS:000418037400002.
   PubMed Web of Science ®Google Scholar
• Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, Gadgeel SM, Hida T, Kowalski DM, Dols MC, et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017;389:255–65. doi:10.1016/s0140-6736(16)32517-x. PMID: WOS:000392801200027.
   PubMed Web of Science ®Google Scholar
• McDermott DF, Huseni MA, Atkins MB, Motzer RJ, Rini BI, Escudier B, Fong L, Joseph RW, Pal SK, Reeves JA, et al. Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma. Nat Med. 2018;24:749–57. doi:10.1038/s41591-018-0053-3. PMID: WOS:000434281300020.
   PubMed Web of Science ®Google Scholar
• Finkelmeier F, Waidmann O, Trojan J. Nivolumab for the treatment of hepatocellular carcinoma. Expert Rev Anticanc. 2018;18:1169–75. doi:10.1080/14737140.2018.1535315. PMID: WOS:000450563700002.
   PubMed Web of Science ®Google Scholar
• Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, Dieras V, Hegg R, Im SA, Wright GS, et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. New Engl J Med. 2018;379:2108–21. doi:10.1056/NEJMoa1809615. PMID: WOS:000451402500006.
   PubMed Web of Science ®Google Scholar
• Rico GT, Price TJ. Atezolizumab for the treatment of colorectal cancer: the latest evidence and clinical potential. Expert Opin Biol Th. 2018;18:449–57. doi:10.1080/14712598.2018.1444024. PMID: WOS:000428249400009.
   PubMed Web of Science ®Google Scholar
• Barlesi F, Vansteenkiste J, Spigel D, Ishii H, Garassino M, de Marinis F, Ozguroglu M, Szczesna A, Polychronis A, Uslu R, et al. Avelumab versus docetaxel in patients with platinum-treated advanced non-small-cell lung cancer (JAVELIN lung 200): an open-label, randomised, phase 3 study. Lancet Oncol. 2018;19:1468–79. doi:10.1016/s1470-2045(18)30673-9. PMID: WOS:000449100300044.
   PubMed Web of Science ®Google Scholar
• Motzer RJ, Penkov K, Haanen J, Rini B, Albiges L, Campbell MT, Venugopal B, Kollmannsberger C, Negrier S, Uemura M, et al. Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. New Engl J Med. 2019;380:1103–15. doi:10.1056/NEJMoa1816047. PMID: WOS:000461898400006.
   PubMed Web of Science ®Google Scholar
• Roviello G, D’Angelo A, Generali D, Pittacolo M, Ganzinelli M, Iezzi G, de Manzini N, Sobhani N. Avelumab in gastric cancer. Immunotherapy-Uk. 2019;11:759–68. doi:10.2217/imt-2019-0011. PMID: WOS:000469496800002.
   PubMed Web of Science ®Google Scholar
• Antonia S, Goldberg SB, Balmanoukian A, Chaft JE, Sanborn RE, Gupta A, Narwal R, Steele K, Gu Y, Karakunnel JJ, et al. Safety and antitumour activity of durvalumab plus tremelimumab in non-small-cell lung cancer: a multicentre, phase 1b study. Lancet Oncol. 2016;17:299–308. doi:10.1016/s1470-2045(15)00544-6. PMID: WOS:000371234900043.
   PubMed Web of Science ®Google Scholar
• Ferris RL, Haddad R, Even C, Tahara M, Dvorkin M, Ciuleanu TE, Clement PM, Mesia R, Kutukova S, Zholudeva L, et al. Durvalumab with or without tremelimumab in patients with recurrent or metastatic head and neck squamous cell carcinoma: EAGLE, a randomized, open -label phase III study. Ann Oncol. 2020;31:942–50. doi:10.1016/j.annonc.2020.04.001. PMID: WOS:000540695500017.
   PubMed Web of Science ®Google Scholar
• Siu LL, Even C, Mesia R, Remenar E, Daste A, Delord JP, Krauss J, Saba NF, Nabell L, Ready NE, et al. Safety and efficacy of durvalumab with or without tremelimumab in patients with PD-L1-low/negative recurrent or metastatic HNSCC the phase 2 CONDOR randomized clinical trial. JAMA Oncol. 2019;5:195–203. doi:10.1001/jamaoncol.2018.4628. PMID: WOS:000458630000015.
   PubMed Web of Science ®Google Scholar
• Shimizu T, Nakajima TE, Yamamoto N, Yonemori K, Koyama T, Kondo S, Sunakawa Y, Izawa N, Horie Y, Xiang SL, et al. Phase I study of envafolimab (KN035), a novel subcutaneous single-domain anti-PD-L1 monoclonal antibody, in Japanese patients with advanced solid tumors. Invest New Drug. 2022;40:1021–31. doi:10.1007/s10637-022-01287-7. PMID: WOS:000836752400001.
   PubMed Web of Science ®Google Scholar
• Shen L, Li J, Deng YH, Zhang WJ, Zhou AP, Guo WJ, Yang JW, Yuan Y, Zhu LJ, Qin SK, et al. Envafolimab (KN035) in advanced tumors with mismatch-repair deficiency. J Clin Onco. 2020;38(15_suppl):3021–3021. doi:10.1200/JCO.2020.38.15_suppl.3021. WOS:000560368301283. PMID: WOS:000560368301283.
   Web of Science ®Google Scholar
• Li J, Deng YH, Zhang WJ, Zhou AP, Guo WJ, Yang JW, Yuan Y, Zhu LJ, Qin SK, Xiang SL, et al. Subcutaneous envafolimab monotherapy in patients with advanced defective mismatch repair/microsatellite instability high solid tumors. J Hematol Oncol. 2021;14:95. doi:10.1186/s13045-021-01095-1. PMID: WOS:000664109200001.
   PubMed Web of Science ®Google Scholar
• Dhillon S, Duggan S. Sugemalimab: first approval. Drugs. 2022;82:593–99. doi:10.1007/s40265-022-01693-4. PMID: WOS:000770214800002.
   PubMedGoogle Scholar
• Ribatti D. Edelman’s view on the discovery of antibodies. Immunol Lett. 2015;164(2):72–75. doi:10.1016/j.imlet.2015.02.005. PMID: WOS:000353094900003.
   PubMed Web of Science ®Google Scholar
• Siegel DL. Recombinant monoclonal antibody technology. Transfus Clin Biol. 2002;9:15–22. doi:10.1016/s1246-7820(01)00210-5. PMID: WOS:000174094300003.
   PubMed Web of Science ®Google Scholar
• Ahmad ZA, Yeap SK, Ali AM, Ho WY, Alitheen NBM, Hamid M. scFv antibody: principles and clinical application. Clin Dev Immunol. 2012;2012:1–15. doi:10.1155/2012/980250. PMID: WOS:000302595700001.
   Google Scholar
• Wen BY, Zhao L, Wang YC, Qiu CN, Xu ZM, Huang KL, Zhu H, Li ZM, Li HJ. Nanobodies targeting the interaction interface of programmed death receptor 1 (PD-1)/PD-1 ligand 1 (PD-1/PD-L1). Prep Biochem Biotech. 2020;50:252–59. doi:10.1080/10826068.2019.1692217. PMID: WOS:000500447300001.
   PubMed Web of Science ®Google Scholar
• Lim H, Chun J, Jin X, Kim J, Yoon J, No KT. Investigation of protein-protein interactions and hot spot region between PD-1 and PD-L1 by fragment molecular orbital method. Sci Rep-Uk. 2019;9:16727. doi:10.1038/s41598-019-53216-z. PMID: WOS:000496135600005.
   PubMed Web of Science ®Google Scholar
• Chen LP. Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity. Nat Rev Immunol. 2004;4:336–47. doi:10.1038/nri1349. PMID: WOS:000221183300012.
   PubMed Web of Science ®Google Scholar
• Xu JM, Shen J, Gu SZ, Zhang Y, Wu LH, Wu J, Shao GL, Zhang YQ, Xu L, Yin T, et al. Camrelizumab in combination with apatinib in patients with advanced hepatocellular carcinoma (RESCUE): a for nonrandomized, open-label, phase II trial. Clin Cancer Res. 2021;27:1003–11. doi:10.1158/1078-0432.Ccr-20-2571. PMID: WOS:000620168400015.
   PubMed Web of Science ®Google Scholar
• Lu M, Zhang PP, Zhang YQ, Li ZW, Gong JF, Li J, Li J, Li Y, Zhang XT, Lu ZH, et al. Efficacy, safety, and biomarkers of toripalimab in patients with recurrent or metastatic neuroendocrine neoplasms: a multiple-center phase Ib trial. Clin Cancer Res. 2020;26:2337–45. doi:10.1158/1078-0432.Ccr-19-4000. PMID: WOS:000535265900008.
   PubMed Web of Science ®Google Scholar
• Tang BX, Yan XQ, Sheng XA, Si L, Cui CL, Kong Y, Mao LL, Lian B, Bai X, Wang X, et al. Safety and clinical activity with an anti-PD-1 antibody JS001 in advanced melanoma or urologic cancer patients. J Hematol Oncol. 2019;12:7. doi:10.1186/s13045-018-0693-2. PMID: WOS:000455639900001.
   PubMed Web of Science ®Google Scholar
• Yang JL, Dong LH, Yang S, Han XH, Han Y, Jiang SY, Yao JR, Zhang ZS, Zhang SX, Liu P, et al. Safety and clinical efficacy of toripalimab, a PD-1 mAb, in patients with advanced or recurrent malignancies in a phase I study. Eur J Cancer. 2020;130:182–92. doi:10.1016/j.ejca.2020.01.028. PMID: WOS:000535711100019.
   PubMed Web of Science ®Google Scholar
• Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, Tykodi SS, Sosman JA, Procopio G, Plimack ER, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. New Engl J Med. 2015;373:1803–13. doi:10.1056/NEJMoa1510665. PMID: WOS:000364144000004.
   PubMed Web of Science ®Google Scholar
• Brahmer J, Reckamp KL, Baas P, Crino L, Eberhardt WEE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. New Engl J Med. 2015;373:123–35. doi:10.1056/NEJMoa1504627. PMID: WOS:000357598600005.
   PubMed Web of Science ®Google Scholar
• Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. New Engl J Med. 2015;373:1627–39. doi:10.1056/NEJMoa1507643. PMID: WOS:000363317800008.
   PubMed Web of Science ®Google Scholar
• Hellmann MD, Ciuleanu TE, Pluzanski A, Lee JS, Otterson GA, Audigier-Valette C, Minenza E, Linardou H, Burgers S, Salman P, et al. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. New Engl J Med. 2018;378:2093–104. doi:10.1056/NEJMoa1801946. PMID: WOS:000433428000007.
   PubMed Web of Science ®Google Scholar
• Overman MJ, McDermott R, Leach JL, Lonardi S, Lenz H-J, Morse MA, Desai J, Hill A, Axelson M, Moss RA, et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017;18:1182–91. doi:10.1016/s1470-2045(17)30422-9. PMID: WOS:000408873500042.
   PubMed Web of Science ®Google Scholar
• El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, Kim TY, Choo SP, Trojan J, Welling TH III, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017;389:2492–502. doi:10.1016/s0140-6736(17)31046-2. PMID: WOS:000403901800028.
   PubMed Web of Science ®Google Scholar
• Johnson D, Balko J, Compton M, Chalkias S, Gorham J, Xu Y, Hicks M, Puzanov I, Alexander M, Bloomer T, et al. Fulminant myocarditis with combination immune checkpoint blockade. New Engl J Med. 2016;375:1749–55. doi:10.1056/NEJMoa1609214. PMID: WOS:000387007300008.
   PubMed Web of Science ®Google Scholar
• Valsecchi ME. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. New Engl J Med. 2015;373:1270–1270. doi:10.1056/NEJMc1509660. PMID: WOS:000361635200016.
   PubMed Web of Science ®Google Scholar
• Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, Patnaik A, Aggarwal C, Gubens M, Horn L, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. New Engl J Med. 2015;372:2018–28. doi:10.1056/NEJMoa1501824. PMID: WOS:000354809300008.
   PubMed Web of Science ®Google Scholar
• Zhu AX, Finn RS, Edeline J, Cattan S, Ogasawara S, Palmer D, Verslype C, Zagonel V, Fartoux L, Vogel A, et al. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Lancet Oncol. 2018;19:940–52. doi:10.1016/s1470-2045(18)30351-6. PMID: WOS:000437342400053.
   PubMed Web of Science ®Google Scholar
• Nanda R, Chow LQM, Dees EC, Berger R, Gupta S, Geva R, Pusztai L, Pathiraja K, Aktan G, Cheng JD, et al. Pembrolizumab in patients with advanced triple-negative breast cancer: phase Ib KEYNOTE-012 study. J Clin Onco. 2016;34:2460–67. doi:10.1200/jco.2015.64.8931. PMID: WOS:000381497000005.
   PubMed Web of Science ®Google Scholar
• Bellmunt J, de Wit R, Vaughn DJ, Fradet Y, Lee JL, Fong L, Vogelzang NJ, Climent MA, Petrylak DP, Choueiri TK, et al. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. New Engl J Med. 2017;376:1015–26. doi:10.1056/NEJMoa1613683. PMID: WOS:000396403700006.
   PubMed Web of Science ®Google Scholar
• Adams S, Schmid P, Rugo HS, Winer EP, Loirat D, Awada A, Cescon DW, Iwata H, Campone M, Nanda R, et al. Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: cohort a of the phase II KEYNOTE-086 study. Ann Oncol. 2019;30:397–404. doi:10.1093/annonc/mdy517. PMID: WOS:000465084000012.
   PubMed Web of Science ®Google Scholar
• Scapin G, Yang X, Prosise WW, McCoy M, Reichert P, Johnston JM, Kashi RS, Strickland C. Structure of full-length human anti-PD1 therapeutic IgG4 antibody pembrolizumab. Nat Struct Molecul Biol. 2015;22:953–58. doi:10.1038/nsmb.3129. PMID: WOS:000366152400007.
   PubMed Web of Science ®Google Scholar
• Zhang T, Song X, Xu L, Ma J, Zhang Y, Gong W, Zhang Y, Zhou X, Wang Z, Wang Y, et al. The binding of an anti-PD-1 antibody to FcγRΙ has a profound impact on its biological functions. Cancer Immunol Immun. 2018;67(7):1079–90. doi:10.1007/s00262-018-2160-x. PMID: WOS:000435591800005.
   PubMed Web of Science ®Google Scholar
• Zhang T, Song XM, Xu LL, Ma J, Zhang YJ, Gong WF, Zhang YL, Zhou XS, Wang ZB, Wang YL, et al. The binding of an anti-PD-1 antibody to FcγRΙ has a profound impact on its biological functions. Cancer Immunol Immun. 2018;67(7):1079–90. doi:10.1007/s00262-018-2160-x. PMID: WOS:000435591800005.
   PubMed Web of Science ®Google Scholar
• Yu R, Wang W, Li T, Li J, Zhao K, Wang W, Liang L, Wu H, Ai T, Huang W, et al. RATIONALE 311: tislelizumab plus concurrent chemoradiotherapy for localized esophageal squamous cell carcinoma. Future Oncol. 2021;17(31):4081–89. doi:10.2217/fon-2021-0632. PMID: WOS:000674048800001.
   PubMed Web of Science ®Google Scholar
• Song Y, Gao Q, Zhang H, Fan L, Zhou J, Zou D, Li W, Yang H, Liu T, Wang Q, et al. Treatment of relapsed or refractory classical Hodgkin lymphoma with the anti-PD-1, tislelizumab: results of a phase 2, single-arm, multicenter study. Leukemia. 2020;34:533–42. doi:10.1038/s41375-019-0545-2. PMID: WOS:000523481800020.
   PubMed Web of Science ®Google Scholar
• Socinski MA, Jotte RM, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N, Rodriguez-Abreu D, Moro-Sibilot D, Thomas CA, Barlesi F, et al. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. New Engl J Med. 2018;378:2288–301. doi:10.1056/NEJMoa1716948. PMID: WOS:000435099900006.
   PubMed Web of Science ®Google Scholar
• Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, Dawson N, O’Donnell PH, Balmanoukian A, Loriot Y, et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016;387:1909–20. doi:10.1016/s0140-6736(16)00561-4. PMID: WOS:000375374200035.
   PubMed Web of Science ®Google Scholar
• Horn L, Mansfield AS, Szczesna A, Havel L, Krzakowski M, Hochmair MJ, Huemer F, Losonczy G, Johnson ML, Nishio M, et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. New Engl J Med. 2018;379:2220–29. doi:10.1056/NEJMoa1809064. PMID: WOS:000452259200007.
   PubMed Web of Science ®Google Scholar
• Herbst RS, Giaccone G, de Marinis F, Reinmuth N, Vergnenegre A, Barrios CH, Morise M, Felip E, Andric Z, Geater S, et al. Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC. New Engl J Med. 2020;383:1328–39. doi:10.1056/NEJMoa1917346. PMID: WOS:000575616600009.
   PubMed Web of Science ®Google Scholar
• Emens LA, Cruz C, Eder JP, Braiteh F, Chung C, Tolaney SM, Kuter I, Nanda R, Cassier PA, Delord JP, et al. Long-term clinical outcomes and biomarker analyses of atezolizumab therapy for patients with metastatic triple-negative breast cancer a phase 1 study. JAMA Oncol. 2019;5:74–82. doi:10.1001/jamaoncol.2018.4224. PMID: WOS:000455776100015.
   PubMed Web of Science ®Google Scholar
• De Meyer T, Muyldermans S, Depicker A. Nanobody-based products as research and diagnostic tools. Trends Biotechnol. 2014;32:263–70. doi:10.1016/j.tibtech.2014.03.001. PMID: WOS:000335625700006.
   PubMed Web of Science ®Google Scholar
• De Genst E, Silence K, Decanniere K, Conrath K, Loris R, Kinne R, Muyldermans S, Wyns L. Molecular basis for the preferential cleft recognition by dromedary heavy-chain antibodies. P Natl Acad Sci Usa. 2006;103:4586–91. doi:10.1073/pnas.0505379103. PMID: WOS:000236362600048.
   PubMed Web of Science ®Google Scholar
• Nguyen VK, Su C, Muyldermans S, van der Loo W. Heavy-chain antibodies in camelidae; a case of evolutionary innovation. Immunogenet. 2002;54:39–47. doi:10.1007/s00251-002-0433-0. PMID: WOS:000175617900005.
   PubMed Web of Science ®Google Scholar
• Barderas R, Desmet J, Timmerman P, Meloen R, Casal JI. Affinity maturation of antibodies assisted by in silico modeling. Proc Natl Acad Sci USA. 2008;105(26):9029–34. doi:10.1073/pnas.0801221105. PMID: WOS:000257354400042.
   PubMed Web of Science ®Google Scholar
• Lippow SM, Wittrup KD, Tidor B. Computational design of antibody-affinity improvement beyond in vivo maturation. Nat Biotechnol. 2007;25:1171–76. doi:10.1038/nbt1336. PMID: WOS:000250226600029.
   PubMed Web of Science ®Google Scholar
• Barderas R, Shochat S, Timmerman P, Hollestelle MJ, Martinez-Torrecuadrada JL, Hoeppener JWM, Altschuh D, Meloen R, Casal JI. Designing antibodies for the inhibition of gastrin activity in tumoral cell lines. Int J Cancer. 2008;122(10):2351–59. doi:10.1002/ijc.23395. PMID: WOS:000254983100024.
   PubMed Web of Science ®Google Scholar
• Lippow SM, Tidor B. Progress in computational protein design. Curr Opin Biotechnol. 2007;18:305–11. doi:10.1016/j.copbio.2007.04.009. PMID: WOS:000249980400003.
   PubMed Web of Science ®Google Scholar
• Shin J, Raissi S, Phelan P, Bullock PA. Rational design of a nivolumab-based ANTI-PD-1 single chain variable fragment that blocks the interaction between PD-1 expressed on T-CELLS and PD-L1 on CHO cells. Protein Expres Purif. 2023;202:106196. doi:10.1016/j.pep.2022.106196. PMID: WOS:000917702900001.
   PubMed Web of Science ®Google Scholar
• Radaev S, Sun P. Recognition of immunoglobulins by Fcγ receptors. Molecular Immunol. 2002;38(14):1073–83. doi:10.1016/s0161-5890(02)00036-6. PMID: WOS:000175986600008.
   PubMed Web of Science ®Google Scholar
• Yamaguchi Y, Barb AW. (2020). A synopsis of recent developments defining how N-glycosylation impacts immunoglobulin G structure and function. Glycobiology, 30(4):214–225. doi:10.1093/glycob/cwz068.
   PubMed Web of Science ®Google Scholar
• Yi M, Zheng XL, Niu MK, Zhu SL, Ge H, Wu KM. Combination strategies with PD-1/PD-L1 blockade: current advances and future directions. Mol Cancer. 2022;21:28. doi:10.1186/s12943-021-01489-2. PMID: WOS:000745440900002.
   PubMed Web of Science ®Google Scholar
• Wang Q, Cao YL, Shen LJ, Xiao TR, Cao RY, Wei SK, Tang M, Du LY, Wu HY, Wu B, et al. Regulation of PD-L1 through direct binding of cholesterol to CRAC motifs. Sci Adv. 2022;8(34):eabq4722. doi:10.1126/sciadv.abq4722. PMID: WOS:000847345000038.
   PubMed Web of Science ®Google Scholar