Novel formats of antibody conjugates: recent advances in payload diversity, conjugation, and linker chemistry

References

• Dumontet C, Reichert JM, Senter PD, et al. Antibody-drug conjugates come of age in oncology. Nat Rev Drug Discov. 2023;22(8):641–661.
   PubMed Web of Science ®Google Scholar
• Qian L, Lin X, Gao X, et al. The dawn of a new era: targeting the “undruggables” with antibody-based therapeutics. Chem Rev. 2023 May 15;123(12):7782–7853. doi: 10.1021/acs.chemrev.2c00915
   PubMed Web of Science ®Google Scholar
• Matsuda Y, Mendelsohn BA. Recent advances in drug-antibody ratio determination of antibody-drug conjugates. Chem Pharm Bull (Tokyo). 2021;69(10):976–983. doi: 10.1248/cpb.c21-00258
   PubMed Web of Science ®Google Scholar
• Li JY, Perry SR, Muniz-Medina V, et al. A biparatopic her2-targeting antibody-drug conjugate induces tumor regression in primary models refractory to or ineligible for HER2-targeted therapy. Cancer Cell. 2016 Jan 11;29(1):117–129. doi: 10.1016/j.ccell.2015.12.008
   PubMed Web of Science ®Google Scholar
• Zhang JH, Shan LL, Liang F, et al. Strategies and considerations for improving recombinant antibody production and quality in Chinese hamster ovary cells. Front Bioeng Biotechnol. 2022;10:856049. doi: 10.3389/fbioe.2022.856049
   PubMed Web of Science ®Google Scholar
• Tawfiq Z, Caiazza NC, Kambourakis S, et al. Synthesis and biological evaluation of antibody drug conjugates based on an antibody expression system: Conamax. ACS Omega. 2020 Apr 7;5(13):7193–7200. doi: 10.1021/acsomega.9b03628
   PubMed Web of Science ®Google Scholar
• Gronemeyer P, Ditz R, Strube J. Trends in upstream and downstream process development for antibody manufacturing. Bioeng (Basel). 2014 Oct 1;1(4):188–212. doi: 10.3390/bioengineering1040188
   PubMedGoogle Scholar
• Matsuda Y, Leung M, Tawfiq Z, et al. In-situ reverse phased HPLC analysis of intact antibody-drug conjugates. Anal Sci. 2021 Aug 10;37(8):1171–1176. doi: 10.2116/analsci.20P424
   PubMed Web of Science ®Google Scholar
• Matsuda Y, Mendelsohn BA. An overview of process development for antibody-drug conjugates produced by chemical conjugation technology. Expert Opin Biol Ther. 2021 Jul;21(7):963–975. doi: 10.1080/14712598.2021.1846714
   PubMed Web of Science ®Google Scholar
• Matsuda Y, Kliman M, Mendelsohn BA. Application of native ion exchange mass spectrometry to intact and subunit analysis of site-specific antibody–drug conjugates produced by AJICAP first generation technology. J Am Soc Mass Spectrom. 2020 Jul 1;31(8):1706–1712. doi: 10.1021/jasms.0c00129
   Web of Science ®Google Scholar
• Tarantino P, Ricciuti B, Pradhan SM, et al. Optimizing the safety of antibody–drug conjugates for patients with solid tumours. Nat Rev Clin Oncol. 2023 Jun 9;20(8):558–576. doi: 10.1038/s41571-023-00783-w
   PubMed Web of Science ®Google Scholar
• Lucas AT, Price LSL, Schorzman AN, et al. Factors affecting the pharmacology of antibody–drug conjugates. Antibodies (Basel). 2018 Feb 7;7(1):10. doi: 10.3390/antib7010010
   PubMedGoogle Scholar
• Cheng-Sanchez I, Moya-Utrera F, Porras-Alcala C, et al. Antibody-drug conjugates containing payloads from marine origin. Mar Drugs. 2022 Jul 30;20(8):494. doi: 10.3390/md20080494
   PubMed Web of Science ®Google Scholar
• AnZicek N, Williams S, Housden MP, et al. Toward aplyronine payloads for antibody-drug conjugates: total synthesis of aplyronines a and D. Org Biomol Chem. 2018 Feb 21;16(8):1343–1350. doi: 10.1039/C7OB03204H
   PubMed Web of Science ®Google Scholar
• Matsuda Y, Endo Y, Saikawa Y, et al. Synthetic studies on polymaxenolides: synthesis and structure elucidation of nominal epoxyafricanane and other africane-type sesquiterpenoids. J Org Chem. 2011 Aug 5;76(15):6258–6263. doi: 10.1021/jo2010186
   PubMed Web of Science ®Google Scholar
• Akaiwa M, Dugal-Tessier J, Mendelsohn BA. Antibody-drug conjugate payloads; study of auristatin derivatives. Chem Pharm Bull (Tokyo). 2020;68(3):201–211. doi: 10.1248/cpb.c19-00853
   PubMed Web of Science ®Google Scholar
• Fu Y, Ho M. DNA damaging agent-based antibody-drug conjugates for cancer therapy. Antibody Therapeutics. 2018;1(2):43–53. doi: 10.1093/abt/tby007
   Google Scholar
• Furqan F, Hamadani M. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma: a review of clinical data. Ther Adv Hematol. 2022;13:20406207221087511. doi: 10.1177/20406207221087511
   Web of Science ®Google Scholar
• Conilh L, Sadilkova L, Viricel W, et al. Payload diversification: a key step in the development of antibody-drug conjugates. J Hematol Oncol. 2023 Jan 17;16(1):3. doi: 10.1186/s13045-022-01397-y
   PubMed Web of Science ®Google Scholar
• Fu Z, Li S, Han S, et al. Antibody drug conjugate: the “biological missile” for targeted cancer therapy. Signal Transduct Target Ther. 2022 Mar 22;7(1):93. doi: 10.1038/s41392-022-00947-7
   PubMed Web of Science ®Google Scholar
• Ashman N, Bargh JD, Spring DR. Non-internalising antibody-drug conjugates. Chem Soc Rev. 2022 Nov 14;51(22):9182–9202. doi: 10.1039/D2CS00446A
   PubMed Web of Science ®Google Scholar
• Wang Z, Li H, Gou L, et al. Antibody–drug conjugates: Recent advances in payloads. Acta Pharm Sin B. 2023;13(10):4025–4059. doi: 10.1016/j.apsb.2023.06.015
   PubMed Web of Science ®Google Scholar
• Fukushima H, Turkbey B, Pinto PA, et al. Near-infrared photoimmunotherapy (NIR-PIT) in urologic cancers. Cancers (Basel). 2022 Jun 17;14(12):2996. doi: 10.3390/cancers14122996
   PubMed Web of Science ®Google Scholar
• Matsuoka K, Yamada M, Sato M, et al. Near-infrared photoimmunotherapy for thoracic cancers: a translational perspective. Biomedicines. 2022 Jul 11;10(7):1662. doi: 10.3390/biomedicines10071662
   PubMed Web of Science ®Google Scholar
• Parakh S, Lee ST, Gan HK, et al. Radiolabeled antibodies for cancer imaging and therapy. Cancers (Basel). 2022 Mar 11;14(6):1454. doi: 10.3390/cancers14061454
   PubMed Web of Science ®Google Scholar
• Matsuda Y, Tawfiq Z, Clancy C, et al. Good manufacturing practice strategy for antibody–drug conjugate synthesis using site-specific chemical conjugation: first-generation AJICAP. ACS Omega. 2019 Nov 26;4(24):20564–20570. doi: 10.1021/acsomega.9b02419
   PubMed Web of Science ®Google Scholar
• Chomet M, van Dongen G, Vugts DJ. State of the art in radiolabeling of antibodies with common and uncommon radiometals for preclinical and clinical immuno-PET. Bioconjug Chem. 2021 Jul 21;32(7):1315–1330. doi: 10.1021/acs.bioconjchem.1c00136
   PubMed Web of Science ®Google Scholar
• Rizzieri DZ. ((R)) (ibritumomab tiuxetan): after more than a decade of treatment experience, what have we learned? Crit Rev Oncol Hematol. 2016 Sep;105:5–17. doi: 10.1016/j.critrevonc.2016.07.008
   PubMed Web of Science ®Google Scholar
• Srinivasan A, Mukherji SK. Tositumomab and iodine I 131 tositumomab (Bexaar). AJNR Am J Neuroradiol. 2011 Apr;32(4):637–638. doi: 10.3174/ajnr.A2593
   PubMed Web of Science ®Google Scholar
• Kolstad A, Illidge T, Bolstad N, et al. Phase 1/2a study of 177Lu-lilotomab satetraxetan in relapsed/refractory indolent non-Hodgkin lymphoma. Blood Adv. 2020 Sep 8;4(17):4091–4101. doi: 10.1182/bloodadvances.2020002583
   PubMed Web of Science ®Google Scholar
• Keam SJ. Lutetium Lu 177 Vipivotide Tetraxetan: First Approval. Mol Diagn Ther. 2022 Jul;26(4):467–475. doi: 10.1007/s40291-022-00594-2
   PubMed Web of Science ®Google Scholar
• Weber WA, Czernin J, Anderson CJ, et al. The Future of Nuclear Medicine, Molecular Imaging, and Theranostics. J Nucl Med. 2020 Dec;61(Suppl Supplement 2):263S–272S. doi: 10.2967/jnumed.120.254532
   PubMedGoogle Scholar
• Lechner VM, Nappi M, Deneny PJ, et al. Visible-light-mediated modification and manipulation of Biomacromolecules. Chem Rev. 2022 Jan 26;122(2):1752–1829. doi: 10.1021/acs.chemrev.1c00357
   PubMed Web of Science ®Google Scholar
• Polito L, Calafato G, Bortolotti M, et al. Antibody conjugates for sarcoma therapy: how far along are we? Biomedicines. 2021 Aug 8;9(8):978. doi: 10.3390/biomedicines9080978
   PubMed Web of Science ®Google Scholar
• Kobayashi H, Choyke PL. Near-infrared photoimmunotherapy of cancer. Acc Chem Res. 2019 Aug 20;52(8):2332–2339. doi: 10.1021/acs.accounts.9b00273
   PubMed Web of Science ®Google Scholar
• Kitamura N, Sento S, Yoshizawa Y, et al. Current Trends and future prospects of molecular targeted therapy in head and neck squamous cell carcinoma. Int J Mol Sci. 2020 Dec 29;22(1):240. doi: 10.3390/ijms22010240
   PubMed Web of Science ®Google Scholar
• Pham TC, Nguyen VN, Choi Y, et al. Recent strategies to develop innovative photosensitizers for enhanced photodynamic therapy. Chem Rev. 2021 Nov 10;121(21):13454–13619. doi: 10.1021/acs.chemrev.1c00381
   PubMed Web of Science ®Google Scholar
• Chalouni C, Doll S. Fate of antibody-drug conjugates in cancer cells. J Exp Clin Cancer Res. 2018 Feb 6;37(1):20. doi: 10.1186/s13046-017-0667-1
   PubMedGoogle Scholar
• Farooq AV, Degli Esposti S, Popat R, et al. Corneal epithelial findings in patients with multiple myeloma treated with antibody-drug conjugate Belantamab Mafodotin in the pivotal, randomized, DREAMM-2 study. Ophthalmol Ther. 2020 Dec;9(4):889–911. doi: 10.1007/s40123-020-00280-8
   PubMed Web of Science ®Google Scholar
• Salifu I, Singh N, Berraondo M, et al. Antibody-drug conjugates, immune-checkpoint inhibitors, and their combination in advanced non-small cell lung cancer. Cancer Treat Res Commun. 2023 Apr 28;36:100713. doi: 10.1016/j.ctarc.2023.100713
   PubMedGoogle Scholar
• Ackerman SE, Pearson CI, Gregorio JD, et al. Immune-stimulating antibody conjugates elicit robust myeloid activation and durable antitumor immunity. Nat Cancer. 2021 Jan;2(1):18–33. doi: 10.1038/s43018-020-00136-x
   PubMedGoogle Scholar
• Kong X, Zuo H, Huang HD, et al. STING as an emerging therapeutic target for drug discovery: perspectives from the global patent landscape. J Adv Res. 2023 Feb;44:119–133.
   PubMed Web of Science ®Google Scholar
• Duvall JR, Thomas JD, Bukhalid RA, et al. Discovery and optimization of a STING agonist platform for application in antibody drug conjugates. J Med Chem. 2023 Jul 24;66(15):10715–10733. doi: 10.1021/acs.jmedchem.3c00907
   PubMed Web of Science ®Google Scholar
• Kieffer ME, Patel AM, Hollingsworth SA, et al. Small molecule agonists of toll-like receptors 7 and 8: a patent review 2014 - 2020. Expert Opin Ther Pat. 2020 Nov;30(11):825–845. doi: 10.1080/13543776.2020.1825687
   PubMed Web of Science ®Google Scholar
• Patinote C, Karroum NB, Moarbess G, et al. Agonist and antagonist ligands of toll-like receptors 7 and 8: ingenious tools for therapeutic purposes. Eur J Med Chem. 2020 May 1;193:112238. doi: 10.1016/j.ejmech.2020.112238
   PubMed Web of Science ®Google Scholar
• Galand C, Venkatraman V, Marques M, et al. 377 AGEN2373 is a CD137 agonist antibody designed to leverage optimal CD137 and FcγR co-targeting to promote antitumor immunologic effects. Regular and young investigator award abstracts. 2020;A229.2–A230.
   Google Scholar
• Liu X, Zhou K, Huang Y, et al. 400 CoupledCARTM technology for treating thyroid cancer. Regular and young investigator award abstracts. 2020;A243–A244.
   Google Scholar
• Imaide S, Riching KM, Makukhin N, et al. Trivalent PROTACs enhance protein degradation via combined avidity and cooperativity. Nat Chem Biol. 2021 Nov;17(11):1157–1167. doi: 10.1038/s41589-021-00878-4
   PubMed Web of Science ®Google Scholar
• Zhou Q. Site-specific antibody conjugation with payloads beyond Cytotoxins. Molecules. 2023 Jan 17;28(3):917. doi: 10.3390/molecules28030917
   PubMed Web of Science ®Google Scholar
• Cotton AD, Nguyen DP, Gramespacher JA, et al. Development of antibody-based PROTACs for the degradation of the cell-surface immune checkpoint protein PD-L1. J Am Chem Soc. 2021 Jan 20;143(2):593–598. doi: 10.1021/jacs.0c10008
   PubMed Web of Science ®Google Scholar
• Momtaz S, Memariani Z, El-Senduny FF, et al. Targeting ubiquitin-proteasome pathway by natural products: novel therapeutic strategy for treatment of neurodegenerative diseases. Front Physiol. 2020;11:11. doi: 10.3389/fphys.2020.00361
   PubMed Web of Science ®Google Scholar
• Brasier AR, Zhou J. Validation of the epigenetic reader bromodomain-containing protein 4 (BRD4) as a therapeutic target for treatment of airway remodeling. Drug Discov Today. 2020 Jan;25(1):126–132. doi: 10.1016/j.drudis.2019.11.002
   PubMed Web of Science ®Google Scholar
• Ahn G, Banik SM, Miller CL, et al. Lytacs that engage the asialoglycoprotein receptor for targeted protein degradation. Nat Chem Biol. 2021 Sep;17(9):937–946. doi: 10.1038/s41589-021-00770-1
   PubMed Web of Science ®Google Scholar
• Zhang X, Liu H, He J, et al. Site-specific chemoenzymatic conjugation of high-affinity M6P glycan ligands to antibodies for targeted protein degradation. ACS Chem Biol. 2022 Nov 18;17(11):3013–3023. doi: 10.1021/acschembio.1c00751
   PubMed Web of Science ®Google Scholar
• Zhang H, Han Y, Yang Y, et al. Covalently engineered nanobody chimeras for targeted membrane protein degradation. J Am Chem Soc. 2021 Oct 13;143(40):16377–16382. doi: 10.1021/jacs.1c08521
   PubMed Web of Science ®Google Scholar
• Peck M, Rothenberg ME, Deng R, et al. A Phase 1, randomized, single-ascending-dose study to investigate the safety, tolerability, and pharmacokinetics of DSTA4637S, an anti-staphylococcus aureus Thiomab antibody-antibiotic conjugate, in healthy volunteers. Antimicrob Agents Chemother. 2019 Jun;63(6). doi: 10.1128/AAC.02588-18
   PubMed Web of Science ®Google Scholar
• Surur AS, Sun D. Macrocycle-antibiotic hybrids: a path to clinical candidates. Front Chem. 2021;9:659845. doi: 10.3389/fchem.2021.659845
   PubMed Web of Science ®Google Scholar
• Hobson AD, McPherson MJ, Hayes ME, et al. Discovery of ABBV-3373, an Anti-TNF Glucocorticoid Receptor Modulator Immunology Antibody Drug Conjugate. J Med Chem. 2022 Dec 8;65(23):15893–15934. doi: 10.1021/acs.jmedchem.2c01579
   PubMed Web of Science ®Google Scholar
• Zhang H, Nimmer PM, Tahir SK, et al. Bcl-2 family proteins are essential for platelet survival. Cell Death Differ. 2007 May;14(5):943–951. doi: 10.1038/sj.cdd.4402081
   PubMed Web of Science ®Google Scholar
• Fairlie WD, Lee EF. Targeting the BCL-2-regulated apoptotic pathway for the treatment of solid cancers. Biochem Soc Trans. 2021 Nov 1;49(5):2397–2410. doi: 10.1042/BST20210750
   PubMed Web of Science ®Google Scholar
• Negi A, Voisin-Chiret AS. Strategies to reduce the on-target platelet toxicity of Bcl-x(L) inhibitors: PROTACs, SNIPERs and prodrug-based approaches. Chembiochem. 2022 Jun 20;23(12):e202100689. doi: 10.1002/cbic.202100689
   PubMed Web of Science ®Google Scholar
• Bohnke N, Berger M, Griebenow N, et al. A novel NAMPT Inhibitor-based antibody-drug conjugate payload class for cancer therapy. Bioconjug Chem. 2022 Jun 15;33(6):1210–1221. doi: 10.1021/acs.bioconjchem.2c00178
   PubMed Web of Science ®Google Scholar
• Lerchen HG, Stelte-Ludwig B, Berndt S, et al. Antibody-prodrug conjugates with KSP inhibitors and legumain-mediated metabolite formation. Chemistry. 2019 Jun 21;25(35):8208–8213. doi: 10.1002/chem.201900441
   PubMed Web of Science ®Google Scholar
• Gentile M, Vasu C, Green A, et al. Targeting colon cancer cells with genistein-17.1A immunoconjugate. Int J Oncol. 2003. doi:10.3892/ijo.22.5.955.
   PubMed Web of Science ®Google Scholar
• Mullard A. Antibody-oligonucleotide conjugates enter the clinic. Nat Rev Drug Discov. 2022 Jan;21(1):6–8. doi: 10.1038/d41573-021-00213-5
   PubMed Web of Science ®Google Scholar
• Dugal-Tessier J, Thirumalairajan S, Jain N. Antibody-Oligonucleotide Conjugates: A Twist to Antibody-Drug Conjugates. J Clin Med. 2021 Feb 18;10(4):838. doi: 10.3390/jcm10040838
   PubMed Web of Science ®Google Scholar
• Pei D, Buyanova M. Overcoming endosomal Entrapment in drug delivery. Bioconjug Chem. 2019 Feb 20;30(2):273–283. doi: 10.1021/acs.bioconjchem.8b00778
   PubMed Web of Science ®Google Scholar
• Malecova B, Burke RS, Cochran M, et al. Targeted tissue delivery of RNA therapeutics using antibody-oligonucleotide conjugates (AOCs). Nucleic Acids Res. 2023 Jul 7;51(12):5901–5910. doi: 10.1093/nar/gkad415
   PubMed Web of Science ®Google Scholar
• Park J, Lim Y, Kang M, et al. P.207 muscle magnetic resonance imaging in myotonic dystrophy type 1: longitudinal study for 5 years. Neuro Disord. 2022;32:S130–S131. doi: 10.1016/j.nmd.2022.07.369
   Web of Science ®Google Scholar
• Samantasinghar A, Sunildutt NP, Ahmed F, et al. A comprehensive review of key factors affecting the efficacy of antibody drug conjugate. Biomed Pharmacother. 2023 May;161:114408.
   PubMed Web of Science ®Google Scholar
• Schwach J, Abdellatif M, Stengl A. More than toxins-current prospects in designing the next generation of antibody drug conjugates. Front Biosci (Landmark Ed). 2022 Aug 12;27(8):240. doi: 10.31083/j.fbl2708240
   PubMed Web of Science ®Google Scholar
• Sadeghian I, Heidari R, Sadeghian S, et al. Potential of cell-penetrating peptides (CPPs) in delivery of antiviral therapeutics and vaccines. Eur J Pharm Sci. 2022 Feb 1;169:106094. doi: 10.1016/j.ejps.2021.106094
   PubMed Web of Science ®Google Scholar
• Nobre CF, Newman MJ, DeLisa A, et al. Moxetumomab pasudotox-tdfk for relapsed/refractory hairy cell leukemia: a review of clinical considerations. Cancer Chemother Pharmacol. 2019 Aug;84(2):255–263. doi: 10.1007/s00280-019-03875-6
   PubMed Web of Science ®Google Scholar
• Neri D. Antibody-cytokine fusions: versatile products for the modulation of anticancer immunity. Cancer Immunol Res. 2019 Mar;7(3):348–354. doi: 10.1158/2326-6066.CIR-18-0622
   PubMed Web of Science ®Google Scholar
• Ji B-J, Song G, Zhang Z, et al. Efficient overexpression of human interleukin-6 in Escherichia coli using nanoluciferase as a fusion partner. Process Biochem. 2015;50(10):1618–1622. doi: 10.1016/j.procbio.2015.06.008
   Web of Science ®Google Scholar
• Shim H. Bispecific antibodies and antibody–drug conjugates for cancer therapy: technological considerations. Biomolecules. 2020 Feb 26;10(3):360. doi: 10.3390/biom10030360
   PubMed Web of Science ®Google Scholar
• Beishenaliev A, Loke YL, Goh SJ, et al. Bispecific antibodies for targeted delivery of anti-cancer therapeutic agents: a review. J Control Release. 2023 Jun 13;359:268–286. doi: 10.1016/j.jconrel.2023.05.032
   PubMed Web of Science ®Google Scholar
• Lucas AT, Moody A, Schorzman AN, et al. Importance and considerations of antibody engineering in antibody-drug conjugates development from a clinical Pharmacologist’s perspective. Antibodies (Basel). 2021 Jul 26;10(3):30. doi: 10.3390/antib10030030
   PubMedGoogle Scholar
• Abdollahpour-Alitappeh M, Lotfinia M, Gharibi T, et al. Antibody-drug conjugates (ADCs) for cancer therapy: strategies, challenges, and successes. J Cell Physiol. 2019 May;234(5):5628–5642. doi: 10.1002/jcp.27419
   PubMed Web of Science ®Google Scholar
• Debon A, Siirola E, Snajdrova R. Enzymatic bioconjugation: a perspective from the pharmaceutical industry. JACS Au. 2023 May 22;3(5):1267–1283. doi: 10.1021/jacsau.2c00617
   PubMedGoogle Scholar
• Yamazaki S, Matsuda Y. Tag‐Free Enzymatic Modification for Antibody−Drug Conjugate Production. ChemistrySelect. 2022;7(48). doi: 10.1002/slct.202203753
   Web of Science ®Google Scholar
• Matsuda Y, Seki T, Yamada K, et al. Chemical site-specific conjugation platform to improve the pharmacokinetics and therapeutic index of antibody-drug conjugates. Mol Pharm. 2021 Nov 1;18(11):4058–4066. doi: 10.1021/acs.molpharmaceut.1c00473
   PubMedGoogle Scholar
• Junutula JR, Raab H, Clark S, et al. Site-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic index. Nat Biotechnol. 2008 Aug;26(8):925–932. doi: 10.1038/nbt.1480
   PubMed Web of Science ®Google Scholar
• Rabuka D, Rush JS, deHart GW, et al. Site-specific chemical protein conjugation using genetically encoded aldehyde tags. Nat Protoc. 2012 May 10;7(6):1052–1067. doi: 10.1038/nprot.2012.045
   PubMed Web of Science ®Google Scholar
• Matsuda Y. Current approaches for the purification of antibody-drug conjugates. J Sep Sci. 2022 Jan;45(1):27–37. doi: 10.1002/jssc.202100575
   PubMed Web of Science ®Google Scholar
• Matsuda Y, Tawfiq Z, Leung M, et al. Insight into temperature dependency and design of experiments towards process development for cysteine‐based antibody‐drug conjugates. ChemistrySelect. 2020;5(28):8435–8439. doi: 10.1002/slct.202001822
   Web of Science ®Google Scholar
• Tawfiq Z, Matsuda Y, Alfonso MJ, et al. Analytical comparison of antibody-drug conjugates based on good manufacturing practice strategies. Anal Sci. 2020 Jul 10;36(7):871–875. doi: 10.2116/analsci.19P465
   PubMed Web of Science ®Google Scholar
• Plyduang T, Arminan A, Movellan J, et al. Polyacetal-based combination therapy for the treatment of prostate cancer. Macromol Rapid Commun. 2018 Oct;39(19):e1800265. doi: 10.1002/marc.201800265
   PubMed Web of Science ®Google Scholar
• Lyon RP, Bovee TD, Doronina SO, et al. Reducing hydrophobicity of homogeneous antibody-drug conjugates improves pharmacokinetics and therapeutic index. Nat Biotechnol. 2015 Jul;33(7):733–735. doi: 10.1038/nbt.3212
   PubMed Web of Science ®Google Scholar
• Toader D, Fessler SP, Collins SD, et al. Discovery and preclinical characterization of XMT-1660, an optimized B7-H4-targeted antibody–drug conjugate for the treatment of cancer. Mol Cancer Ther. 2023 Jun 9;22(9):999–1012. doi: 10.1158/1535-7163.MCT-22-0786
   PubMed Web of Science ®Google Scholar
• Nakada T, Masuda T, Naito H, et al. Novel antibody drug conjugates containing exatecan derivative-based cytotoxic payloads. Bioorg Med Chem Lett. 2016 Mar 15;26(6):1542–1545. doi: 10.1016/j.bmcl.2016.02.020
   PubMed Web of Science ®Google Scholar
• Goldenberg DM, Sharkey RM. Sacituzumab govitecan, a novel, third-generation, antibody-drug conjugate (ADC) for cancer therapy. Expert Opin Biol Ther. 2020 Aug;20(8):871–885. doi: 10.1080/14712598.2020.1757067
   PubMed Web of Science ®Google Scholar
• Dovgan I, Ehkirch A, Lehot V, et al. On the use of DNA as a linker in antibody-drug conjugates: synthesis, stability and in vitro potency. Sci Rep. 2020 May 6;10(1):7691. doi: 10.1038/s41598-020-64518-y
   PubMed Web of Science ®Google Scholar
• Valliere-Douglass JF, Hengel SM, Pan LY. Approaches to interchain cysteine-linked ADC characterization by mass spectrometry. Mol Pharm. 2015 Jun 1;12(6):1774–1783. doi: 10.1021/mp500614p
   PubMedGoogle Scholar
• Fujii T, Reiling C, Quinn C, et al. Physical characteristics comparison between maytansinoid-based and auristatin-based antibody-drug conjugates. Explor Target Antitumor Ther. 2021;2(6):576–585. doi: 10.37349/etat.2021.00064
   PubMedGoogle Scholar
• Matsuda Y, Leung M, Okuzumi T, et al. A purification strategy utilizing hydrophobic interaction chromatography to obtain homogeneous species from a site-specific antibody drug conjugate produced by AJICAP™ first generation. Antibodies (Basel). 2020 May 18;9(2):16. doi: 10.3390/antib9020016
   PubMedGoogle Scholar
• Yamazaki S, Shikida N, Takahashi K, et al. Lipoate-acid ligase a modification of native antibody: synthesis and conjugation site analysis. Bioorg Med Chem Lett. 2021 Nov 1;51:128360. doi: 10.1016/j.bmcl.2021.128360
   PubMed Web of Science ®Google Scholar
• Matsuda Y, Malinao MC, Robles V, et al. Proof of site-specificity of antibody-drug conjugates produced by chemical conjugation technology: AJICAP first generation. J Chromatogr B Analyt Technol Biomed Life Sci. 2020 Mar 1;1140:121981. doi: 10.1016/j.jchromb.2020.121981
   PubMed Web of Science ®Google Scholar
• Rashidian M, Dozier JK, Distefano MD. Enzymatic labeling of proteins: techniques and approaches. Bioconjug Chem. 2013 Aug 21;24(8):1277–1294. doi: 10.1021/bc400102w
   PubMed Web of Science ®Google Scholar
• Choi CR, Rhee HW. Proximity labeling: an enzymatic tool for spatial biology. Trends Biotechnol. 2022 Feb;40(2):145–148. doi: 10.1016/j.tibtech.2021.09.008
   PubMed Web of Science ®Google Scholar
• Ellerman D, Scheer JM. Generation of bispecific antibodies by chemical conjugation. Bispecific Antibodies. 2011;47–63.
   Google Scholar
• Szijj P, Chudasama V. The renaissance of chemically generated bispecific antibodies. Nat Rev Chem. 2021 Feb;5(2):78–92. doi: 10.1038/s41570-020-00241-6
   PubMed Web of Science ®Google Scholar
• Dimasi N, Kumar A, Gao C. Generation of bispecific antibodies using chemical conjugation methods. Drug Discov Today Technol. 2021 Dec;40:13–24. doi: 10.1016/j.ddtec.2021.08.006
   PubMedGoogle Scholar
• You J, Zhang J, Wang J, et al. Cysteine-based coupling: challenges and solutions. Bioconjug Chem. 2021 Aug 18;32(8):1525–1534. doi: 10.1021/acs.bioconjchem.1c00213
   PubMed Web of Science ®Google Scholar
• Underwood DJ, Bettencourt J, Jawad Z. The manufacturing considerations of bispecific antibodies. Expert Opin Biol Ther. 2022 Aug;22(8):1043–1065. doi: 10.1080/14712598.2022.2095900
   PubMed Web of Science ®Google Scholar
• Matsuda Y, Yamada K, Okuzumi T, et al. Gram-Scale antibody–drug conjugate synthesis by site-specific chemical conjugation: AJICAP first generation. Org Process Res Dev. 2019;23(12):2647–2654. doi: 10.1021/acs.oprd.9b00316
   Web of Science ®Google Scholar
• Nakahara Y, Mendelsohn BA, Matsuda Y. Antibody–drug conjugate synthesis using continuous flow microreactor technology. Org Process Res Dev. 2022;26(9):2766–2770. doi: 10.1021/acs.oprd.2c00217
   Web of Science ®Google Scholar
• Taylor RJ, Geeson MB, Journeaux T, et al. Chemical and enzymatic methods for post-translational protein-protein conjugation. J Am Chem Soc. 2022 Aug 17;144(32):14404–14419. doi: 10.1021/jacs.2c00129
   PubMed Web of Science ®Google Scholar
• Yuan D, Zhang Y, Lim KH, et al. Site-Selective Lysine Acetylation of Human Immunoglobulin G for Immunoliposomes and Bispecific Antibody Complexes. J Am Chem Soc. 2022 Oct 12;144(40):18494–18503. doi: 10.1021/jacs.2c07594
   PubMedGoogle Scholar
• Thoreau F, Szijj PA, Greene MK, et al. Modular chemical construction of IgG-like mono- and bispecific synthetic antibodies (SynAbs). ACS Cent Sci. 2023 Mar 22;9(3):476–487. doi: 10.1021/acscentsci.2c01437
   PubMed Web of Science ®Google Scholar
• Szijj PA, Gray MA, Ribi MK, et al. Chemical generation of checkpoint inhibitory T cell engagers for the treatment of cancer. Nat Chem. 2023 Jul 24. doi: 10.1038/s41557-023-01280-4
   Web of Science ®Google Scholar
• Lee T, Kim JH, Kwon SJ, et al. Site-selective antibody–drug conjugation by a proximity-driven S to N acyl transfer reaction on a therapeutic antibody. J Med Chem. 2022;65(7):5751–5759. doi: 10.1021/acs.jmedchem.2c00084
   PubMed Web of Science ®Google Scholar
• Zeng Y, Shi W, Dong Q, et al. A traceless site‐specific conjugation on native antibodies enables efficient One‐Step payload assembly. Angewandte Chemie. 2022;61(36):e202204132. doi: 10.1002/anie.202204132
   Google Scholar
• Yang Y, Song Z, Tian T, et al. Trimming crystallizable fragment (Fc) glycans enables the direct enzymatic transfer of biomacromolecules to antibodies as therapeutics. Angewandte Chemie. 2023;62(36):e202308174. doi: 10.1002/anie.202308174
   Google Scholar
• Fujii T, Matsuda Y, Seki T, et al. AJICAP second generation: improved chemical site-specific conjugation technology for antibody-drug conjugate production. Bioconjug Chem. 2023 Mar 9;34(4):728–738.
   PubMed Web of Science ®Google Scholar
• Watanabe T, Fujii T, Stofleth JT, et al. Scale-up synthesis of site-specific antibody–drug conjugates using AJICAP second-generation technology. Org Process Res Dev. 2023;27(6):1136–1143. doi: 10.1021/acs.oprd.3c00111
   Web of Science ®Google Scholar
• Fujii T, Ito K, Takahashi K, et al. Bispecific antibodies produced via chemical site-specific conjugation technology: AJICAP second generation. ChemRxiv. 2023. doi: 10.26434/chemrxiv-2023-9p5p7
   Google Scholar
• Matsuda Y, Chakrabarti A, Takahashi K, et al. Chromatographic analysis of site-specific antibody-drug conjugates produced by AJICAP first-generation technology using a recombinant FcgammaIIIa receptor-ligand affinity column. J Chromatogr B Analyt Technol Biomed Life Sci. 2021 Jul 1;1177:122753. doi: 10.1016/j.jchromb.2021.122753
   PubMed Web of Science ®Google Scholar
• Weddell J, Chiney MS, Bhatnagar S, et al. Mechanistic modeling of intra-tumor spatial distribution of antibody-drug conjugates: insights into dosing strategies in oncology. Clin Transl Sci. 2021 Jan;14(1):395–404. doi: 10.1111/cts.12892
   PubMed Web of Science ®Google Scholar
• Pillow TH, Adhikari P, Blake RA, et al. Antibody conjugation of a chimeric BET degrader enables in vivo activity. Chembiochem. 2020 Jan 7;15(1):17–25. doi: 10.1002/cmdc.201900497
   Google Scholar
• Hartley JA. Antibody-drug conjugates (ADCs) delivering pyrrolobenzodiazepine (PBD) dimers for cancer therapy. Expert Opin Biol Ther. 2021 Jul;21(7):931–943. doi: 10.1080/14712598.2020.1776255
   PubMed Web of Science ®Google Scholar
• Dorywalska M, Dushin R, Moine L, et al. Molecular basis of valine-citrulline-PABC linker instability in site-specific ADCs and its mitigation by linker Design. Mol Cancer Ther. 2016 May;15(5):958–970. doi: 10.1158/1535-7163.MCT-15-1004
   PubMed Web of Science ®Google Scholar
• Zhao H, Gulesserian S, Malinao MC, et al. A potential mechanism for ADC-Induced neutropenia: role of neutrophils in their own demise. Mol Cancer Ther. 2017 Sep;16(9):1866–1876. doi: 10.1158/1535-7163.MCT-17-0133
   PubMed Web of Science ®Google Scholar
• Miller JT, Vitro CN, Fang S, et al. Enzyme-Agnostic Lysosomal Screen Identifies New Legumain-Cleavable ADC Linkers. Bioconjug Chem. 2021 Apr 21;32(4):842–858. doi: 10.1021/acs.bioconjchem.1c00124
   PubMed Web of Science ®Google Scholar
• Anami Y, Yamazaki CM, Xiong W, et al. Glutamic acid-valine-citrulline linkers ensure stability and efficacy of antibody-drug conjugates in mice. Nat Commun. 2018 Jun 28;9(1):2512. doi: 10.1038/s41467-018-04982-3
   PubMedGoogle Scholar
• SYY H, Anami Y, Yamazaki CM, et al. An Enzymatically Cleavable Tripeptide Linker for maximizing the therapeutic index of antibody-drug conjugates. Mol Cancer Ther. 2022 Sep 6;21(9):1449–1461. doi: 10.1158/1535-7163.MCT-22-0362
   PubMed Web of Science ®Google Scholar
• Chuprakov S, Ogunkoya AO, Barfield RM, et al. Tandem-cleavage linkers improve the in vivo stability and tolerability of antibody-drug conjugates. Bioconjug Chem. 2021 Apr 21;32(4):746–754. doi: 10.1021/acs.bioconjchem.1c00029
   PubMed Web of Science ®Google Scholar
• Watanabe T, Arashida N, Fujii T, et al. Exo-cleavable linkers: a paradigm shift for enhanced stability and therapeutic efficacy in antibody-drug conjugates. 2023. ChemRxiv. 2023. doi: 10.26434/chemrxiv-2023-hn02p
   Google Scholar
• Poudel YB, Chowdari NS, Cheng H, et al. Chemical modification of linkers provides stable linker-payloads for the generation of antibody-drug conjugates. ACS Med Chem Lett. 2020 Nov 12;11(11):2190–2194. doi: 10.1021/acsmedchemlett.0c00325
   PubMed Web of Science ®Google Scholar
• Love EA, Sattikar A, Cook H, et al. Developing an antibody-drug conjugate approach to selective inhibition of an extracellular protein. Chembiochem. 2019 Mar 15;20(6):754–758. doi: 10.1002/cbic.201800623
   PubMed Web of Science ®Google Scholar
• Fuchigami H, Manabe S, Yasunaga M, et al. Chemotherapy payload of anti-insoluble fibrin antibody-drug conjugate is released specifically upon binding to fibrin. Sci Rep. 2018 Sep 21;8(1):14211. doi: 10.1038/s41598-018-32601-0
   PubMedGoogle Scholar
• Poreba M. Protease-activated prodrugs: strategies, challenges, and future directions. FEBS J. 2020 May;287(10):1936–1969. doi: 10.1111/febs.15227
   PubMed Web of Science ®Google Scholar
• Candelaria PV, Leoh LS, Penichet ML, et al. Antibodies targeting the transferrin receptor 1 (TfR1) as direct anti-cancer agents. Front Immunol. 2021;12:607692. doi: 10.3389/fimmu.2021.607692
   PubMed Web of Science ®Google Scholar
• Smeenk M, Agramunt J, Bonger KM. Recent developments in bioorthogonal chemistry and the orthogonality within. Curr Opin Chem Biol. 2021 Feb;60:79–88. doi: 10.1016/j.cbpa.2020.09.002
   PubMedGoogle Scholar
• Baalmann M, Neises L, Bitsch S, et al. A bioorthogonal Click chemistry toolbox for targeted synthesis of branched and well-defined protein-protein conjugates. Angew Chem Int Ed Engl. 2020 Jul 27;59(31):12885–12893. doi: 10.1002/anie.201915079
   PubMed Web of Science ®Google Scholar
• Szijj PA, Bahou C, Chudasama V. Minireview: addressing the retro-Michael instability of maleimide bioconjugates. Drug Discov Today Technol. 2018 Dec;30:27–34. doi: 10.1016/j.ddtec.2018.07.002
   PubMedGoogle Scholar
• Erian A, Sherif S, Gaber H. The chemistry of α-haloketones and their utility in heterocyclic synthesis. Molecules. 2003;8(11):793–865. doi: 10.3390/81100793
   Web of Science ®Google Scholar
• Yang C, He B, Zhang H, et al. IgG Fc affinity ligands and their applications in antibody-involved drug delivery: a brief review. Pharmaceutics. 2023;15(1):187. doi: 10.3390/pharmaceutics15010187
   PubMed Web of Science ®Google Scholar
• Giese M, Davis PD, Woodman RH, et al. Linker Architectures as steric auxiliaries for altering enzyme-mediated payload release from bioconjugates. Bioconjug Chem. 2021 Oct 20;32(10):2257–2267. doi: 10.1021/acs.bioconjchem.1c00429
   PubMed Web of Science ®Google Scholar
• Viricel W, Fournet G, Beaumel S, et al. Monodisperse polysarcosine-based highly-loaded antibody-drug conjugates. Chem Sci. 2019 Apr 14;10(14):4048–4053. doi: 10.1039/C9SC00285E
   PubMed Web of Science ®Google Scholar
• Evans N, Grygorash R, Williams P, et al. Incorporation of hydrophilic macrocycles into drug-linker reagents produces antibody-drug conjugates with enhanced in vivo performance. Front Pharmacol. 2022;13:764540. doi: 10.3389/fphar.2022.764540
   PubMed Web of Science ®Google Scholar
• Haeckel A, Appler F, Ariza de Schellenberger A, et al. XTEN as biological alternative to PEGylation allows complete expression of a protease-activatable killin-based cytostatic. PLoS One. 2016;11(6):e0157193. doi: 10.1371/journal.pone.0157193
   PubMed Web of Science ®Google Scholar