Antibody drug conjugates for glioblastoma: current progress towards clinical use

References

• Miller KD, Ostrom QT, Kruchko C, et al. Brain and other central nervous system tumor statistics, 2021. CA Cancer J Clin. 2021;71(5):381–406. doi: 10.3322/caac.21693
   PubMed Web of Science ®Google Scholar
• Australian Institute of Health and Welfare. Brain and other central nervous system cancers. Cat. no. CAN 106. Canberra: AIHW; 2017.
   Google Scholar
• Ostrom QT, Price M, Neff C, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2015–2019. Neuro Oncol. 2022;24(Supplement_5):v1–v95. doi: 10.1093/neuonc/noac202
   PubMedGoogle Scholar
• Miller KD, Ostrom QT, Kruchko C, et al. Brain and other central nervous system tumor statistics, 2021. CA Cancer J Clin N/A(n/A). 2021;71(5):381–406. doi: 10.3322/caac.21693
   PubMed Web of Science ®Google Scholar
• Louis DN, Perry A, Wesseling P, et al. The 2021 WHO classification of tumors of the central nervous system: a summary. Neurooncol. 2021 Aug 2;23(8):1231–1251. doi: 10.1093/neuonc/noab106
   Google Scholar
• Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987–996. doi: 10.1056/NEJMoa043330
   PubMed Web of Science ®Google Scholar
• Stupp R, Taillibert S, Kanner A, et al. Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: a randomized clinical trialEffect of TTFields Plus Temozolomide vs Temozolomide Alone on GlioblastomaEffect of TTFields Plus Temozolomide vs Temozolomide Alone on Glioblastoma. JAMA. 2017;318(23):2306–2316. doi: 10.1001/jama.2017.18718
   PubMed Web of Science ®Google Scholar
• Wong ET, Hess KR, Gleason MJ, et al. Outcomes and prognostic factors in recurrent glioma patients enrolled onto phase II clinical trials. J Clin Oncol. 1999 Aug;17(8):2572–2578. doi: 10.1200/JCO.1999.17.8.2572
   PubMed Web of Science ®Google Scholar
• van den Bent MJ, Brandes AA, Rampling R, et al. Randomized phase II trial of erlotinib versus temozolomide or carmustine in recurrent glioblastoma: EORTC brain tumor group study 26034. J Clin Oncol. 2009 Mar 10;27(8):1268–1274. doi: 10.1200/JCO.2008.17.5984
   PubMed Web of Science ®Google Scholar
• Batchelor TT, Mulholland P, Neyns B, et al. Phase III randomized trial comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, versus lomustine alone in patients with recurrent glioblastoma. J Clin Oncol. 2013;31(26):3212–3218. doi: 10.1200/JCO.2012.47.2464
   PubMed Web of Science ®Google Scholar
• Wick W, Puduvalli VK, Chamberlain MC, et al. Phase III study of enzastaurin compared with lomustine in the treatment of recurrent intracranial glioblastoma. J Clin Oncol. 2010;28(7):1168–1174. doi: 10.1200/JCO.2009.23.2595
   PubMed Web of Science ®Google Scholar
• Taal W, Oosterkamp HM, Walenkamp AME, et al. Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomised controlled phase 2 trial. Lancet Oncol. 2014;15(9):943–953. doi: 10.1016/S1470-2045(14)70314-6
   PubMed Web of Science ®Google Scholar
• Dumontet C, Reichert JM, Senter PD, et al. Antibody-drug conjugates come of age in oncology. Nat Rev Drug Discov. 2023 Jun 12;12:12.
   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 09;9:09.
   Google Scholar
• Mair MJ, Bartsch R, Le Rhun E, et al. Understanding the activity of antibody-drug conjugates in primary and secondary brain tumours. Nat Rev Clin Oncol. 2023 06;20(6):372–389. doi: 10.1038/s41571-023-00756-z
   PubMed Web of Science ®Google Scholar
• Kunwar S, Chang S, Westphal M, et al. Phase III randomized trial of CED of IL13-PE38QQR vs gliadel wafers for recurrent glioblastoma. Neuro Oncol. 2010;12(8):871–881. doi: 10.1093/neuonc/nop054
   PubMed Web of Science ®Google Scholar
• Weber F, Asher A, Bucholz R, et al. Safety, tolerability, and tumor response of IL4-Pseudomonas exotoxin (NBI-3001) in patients with recurrent malignant glioma. J Neurooncol. 2003 Aug;64(1–2):125–137. doi: 10.1007/BF02700027
   PubMed Web of Science ®Google Scholar
• Sampson JH, Akabani G, Archer GE, et al. Intracerebral infusion of an EGFR-targeted toxin in recurrent malignant brain tumors. Neuro Oncol. 2008 Jun;10(3):320–329. doi: 10.1215/15228517-2008-012
   PubMed Web of Science ®Google Scholar
• Weaver M, Laske DW. Transferrin receptor ligand-targeted toxin conjugate (Tf-CRM107) for therapy of malignant gliomas. J Neurooncol. 2003 Oct;65(1):3–13. doi: 10.1023/A:1026246500788
   PubMed Web of Science ®Google Scholar
• Gan HK, Cvrljevic AN, Johns TG. The epidermal growth factor receptor variant III (EGFRvIII): where wild things are altered. FEBS J. 2013 Nov;280(21):5350–5370. doi: 10.1111/febs.12393
   PubMed Web of Science ®Google Scholar
• Chandramohan V, Sampson JH, Pastan I, et al. Toxin-based targeted therapy for malignant brain tumors. Clin Dev Immunol. 2012;2012:15. doi: 10.1155/2012/480429
   Google Scholar
• Tortorella S, Karagiannis TC. Transferrin receptor-mediated endocytosis: a useful target for cancer therapy. J Membr Biol. 2014 Apr;247(4):291–307. doi: 10.1007/s00232-014-9637-0
   PubMed Web of Science ®Google Scholar
• Rand RW, Kreitman RJ, Patronas N, et al. Intratumoral administration of recombinant circularly permuted interleukin-4-pseudomonas exotoxin in patients with high-grade glioma. Clin Cancer Res. 2000 Jun;6(6):2157–2165.
   PubMed Web of Science ®Google Scholar
• Joshi BH, Leland P, Asher A, et al. In situ expression of interleukin-4 (IL-4) receptors in human brain tumors and cytotoxicity of a recombinant IL-4 cytotoxin in primary glioblastoma cell cultures. Cancer Res. 2001 Nov 15;61(22):8058–8061.
   PubMed Web of Science ®Google Scholar
• Sampson JH, Singh Achrol A, Aghi MK, et al. Targeting the IL4 receptor with MDNA55 in patients with recurrent glioblastoma: results of a phase IIb trial. Neurooncol. 2023 Jun 2;25(6):1085–1097. doi: 10.1093/neuonc/noac285
   Google Scholar
• Gan HK, Burgess AW, Clayton AH, et al. Targeting of a conformationally exposed, tumor-specific epitope of EGFR as a strategy for cancer therapy. Cancer Res. 2012 Jun 15;72(12):2924–2930. doi: 10.1158/0008-5472.CAN-11-3898
   PubMed Web of Science ®Google Scholar
• Phillips AC, Boghaert ER, Vaidya KS, et al. ABT-414, an antibody-drug conjugate targeting a tumor-selective EGFR Epitope. Mol Cancer Ther. 2016 Apr;15(4):661–669. doi: 10.1158/1535-7163.MCT-15-0901
   PubMed Web of Science ®Google Scholar
• Reardon DA, Lassman AB, van den Bent M, et al. Efficacy and safety results of ABT-414 in combination with radiation and temozolomide in newly diagnosed glioblastoma. Neurooncol. 2017 Jul 1;19(7):965–975. doi: 10.1093/neuonc/now257
   Google Scholar
• van den Bent M, Gan HK, Lassman AB, et al. Efficacy of depatuxizumab mafodotin (ABT-414) monotherapy in patients with EGFR-amplified, recurrent glioblastoma: results from a multi-center, international study. Cancer Chemother Pharmacol. 2017 Dec;80(6):1209–1217. doi: 10.1007/s00280-017-3451-1
   PubMed Web of Science ®Google Scholar
• Gan HK, Reardon DA, Lassman AB, et al. Safety, pharmacokinetics and antitumor response of ABT-414 as monotherapy or as combination therapy with temozolomide in patients with glioblastoma. Neuro Oncol. 2016;18(20):838–847. doi: 10.1093/neuonc/nox202
   Google Scholar
• Richardson DL. Ocular toxicity and mitigation strategies for antibody drug conjugates in gynecologic oncology. Gynecol Oncol Rep. 2023 Apr 01;46:101148. doi: 10.1016/j.gore.2023.101148
   PubMed Web of Science ®Google Scholar
• Lassman AB, Pugh SL, Wang TJC, et al. Depatuxizumab mafodotin in EGFR-amplified newly diagnosed glioblastoma: a phase III randomized clinical trial. Neurooncol. 2023 Feb 14;25(2):339–350. doi: 10.1093/neuonc/noac173
   Google Scholar
• Van Den Bent M, Eoli M, Sepulveda JM, et al. INTELLANCE 2/EORTC 1410 randomized phase II study of depatux-M alone and with temozolomide vs temozolomide or lomustine in recurrent EGFR amplified glioblastoma. Neuro-Oncologyquery. 2020;22(5):684–693. doi: 10.1093/neuonc/noz222
   PubMed Web of Science ®Google Scholar
• Narita Y, Muragaki Y, Kagawa N, et al. Safety and efficacy of depatuxizumab mafodotin in Japanese patients with malignant glioma: a nonrandomized, phase 1/2 trial. Cancer Sci. 2021 Dec;112(12):5020–5033. doi: 10.1111/cas.15153
   PubMed Web of Science ®Google Scholar
• Padovan M, Eoli M, Pellerino A, et al. Depatuxizumab mafodotin (Depatux-M) plus temozolomide in recurrent glioblastoma patients: real-world Experience from a Multicenter Study of Italian Association of Neuro-Oncology (AINO). Cancers (Basel). 2021 Jun 3;13(11):2773. doi: 10.3390/cancers13112773
   PubMed Web of Science ®Google Scholar
• Carneiro BA, Papadopoulos KP, Strickler JH, et al. Phase I study of anti-epidermal growth factor receptor antibody-drug conjugate serclutamab talirine: safety, pharmacokinetics, and antitumor activity in advanced glioblastoma. Neurooncol Adv. 2023 Jan;5(1):vdac183. doi: 10.1093/noajnl/vdac183
   PubMedGoogle Scholar
• Hamblett KJ, Kozlosky CJ, Siu S, et al. AMG 595, an Anti-EGFRvIII Antibody–Drug Conjugate, Induces Potent Antitumor Activity against EGFRvIII-Expressing Glioblastoma. Mol Cancer Ther. 2015;14(7):1614–1624. molcanther. 1078.2014. doi: 10.1158/1535-7163.MCT-14-1078
   PubMed Web of Science ®Google Scholar
• Rosenthal M, Curry R, Reardon DA, et al. Safety, tolerability, and pharmacokinetics of anti-EGFRvIII antibody–drug conjugate AMG 595 in patients with recurrent malignant glioma expressing EGFRvIII. Cancer Chemother Pharmacol. 2019;84(2):327–336. doi: 10.1007/s00280-019-03879-2
   PubMed Web of Science ®Google Scholar
• Gan HK, Parakh S, Lassman AB, et al. Tumor volumes as a predictor of response to the anti-EGFR antibody drug conjugate depatuxizumab mafadotin. Neurooncol Adv. 2021 Aug 3:3(1). doi: 10.1093/noajnl/vdab102
   Google Scholar
• Marin BM, Porath KA, Jain S, et al. Heterogeneous delivery across the blood-brain barrier limits the efficacy of an EGFR-targeting antibody drug conjugate in glioblastoma. Neuro Oncol. 2021 May 29;23(12):2042–2053. doi: 10.1093/neuonc/noab133
   PubMed Web of Science ®Google Scholar
• Porath KA, Regan MS, Griffith JI, et al. Convection enhanced delivery of EGFR targeting antibody-drug conjugates serclutamab talirine and depatux-M in glioblastoma patient-derived xenografts. Neurooncol Adv. 2022 Jan;4(1):vdac130. doi: 10.1093/noajnl/vdac130
   PubMedGoogle Scholar
• Anami Y, Otani Y, Xiong W, et al. Homogeneity of antibody-drug conjugates critically impacts the therapeutic efficacy in brain tumors. Cell Rep. 2022;39(8):110839. doi: 10.1016/j.celrep.2022.110839
   PubMed Web of Science ®Google Scholar
• Lassman AB, van den Bent MJ, Gan HK, et al. Safety and efficacy of depatuxizumab mafodotin + temozolomide in patients with EGFR-amplified, recurrent glioblastoma: results from an international phase I multicenter trial. Neurooncol. 2019 Jan 1;21(1):106–114. doi: 10.1093/neuonc/noy091
   Google Scholar
• Lassman AB, Roberts-Rapp L, He L, et al. P01.071 genomic profiling identifies tubulin mutations that may predict response to depatuxizumab mafodotin in patients with glioblastoma. Neuro Oncol. 2018;20(suppl_3):iii246–iii246. doi: 10.1093/neuonc/noy139.113
   Google Scholar
• Abbott NJ, Patabendige AA, Dolman DE, et al. Structure and function of the blood–brain barrier. Neurobiol Dis. 2010;37(1):13–25. doi: 10.1016/j.nbd.2009.07.030
   PubMed Web of Science ®Google Scholar
• Sarkaria JN, Hu LS, Parney IF, et al. Is the blood–brain barrier really disrupted in all glioblastomas? A critical assessment of existing clinical data. Neuro Oncol. 2018;20(2):184–191. doi: 10.1093/neuonc/nox175
   PubMed Web of Science ®Google Scholar
• Chudasama V, Maruani A, Caddick S. Recent advances in the construction of antibody–drug conjugates. Nat Chem. 2016 Jan 02;8(2):114–119.
   PubMed Web of Science ®Google Scholar
• Gong HH, Ihle N, Jones MT, et al. Control Strategy for Small Molecule Impurities in Antibody-Drug Conjugates. AAPS Pharm Sci Tech. 2018 Apr 01;19(3):971–977. doi: 10.1208/s12249-017-0943-6
   PubMed Web of Science ®Google Scholar
• MCNeill KA, Fine H. Challenges in clinical trial design for recurrent glioblastoma. Clin Investig. 2013;3(9):835–848. doi: 10.4155/cli.13.67
   Google Scholar
• Gan HK, van den Bent M, Lassman AB, et al. Antibody-drug conjugates in glioblastoma therapy: the right drugs to the right cells. Nat Rev Clin Oncol. 2017 Nov;14(11):695–707. doi: 10.1038/nrclinonc.2017.95
   PubMed Web of Science ®Google Scholar
• Roberts JW, Powlovich L, Sheybani N, et al. Focused ultrasound for the treatment of glioblastoma. J Neurooncol. 2022 Apr;157(2):237–247. doi: 10.1007/s11060-022-03974-0
   PubMed Web of Science ®Google Scholar
• Phoenix TN, Patmore DM, Boop S, et al. Medulloblastoma genotype dictates blood brain barrier phenotype. Cancer Cell. 2016 Apr 11;29(4):508–522. doi: 10.1016/j.ccell.2016.03.002
   PubMed Web of Science ®Google Scholar
• He L, Zhou H, Zeng Z, et al. Wnt/β-catenin signaling cascade: a promising target for glioma therapy. J Cell Physiol. 2019;234(3):2217–2228. doi: 10.1002/jcp.27186
   PubMed Web of Science ®Google Scholar
• Wang W, He H, Marin-Ramos NI, et al. Enhanced brain delivery and therapeutic activity of trastuzumab after blood-brain barrier opening by NEO100 in mouse models of brain-metastatic breast cancer. Neurooncol. 2021;23(12):2123–2123. In press. doi: 10.1093/neuonc/noab204
   Google Scholar
• Nicolazzo JA, Katneni K. Drug transport across the blood-brain barrier and the impact of breast cancer resistance protein (ABCG2). Curr Top Med Chem. 2009;9(2):130–147. doi: 10.2174/156802609787521580
   PubMed Web of Science ®Google Scholar
• Hafeez U, Parakh S, Gan HK, et al. Antibody–drug conjugates for Cancer therapy. Molecules. 2020;25(20):4764. doi: 10.3390/molecules25204764
   PubMed Web of Science ®Google Scholar
• Agarwal S, Mittapalli RK, Zellmer DM, et al. Active efflux of dasatinib from the brain limits efficacy against murine glioblastoma: broad implications for the clinical use of molecularly targeted agents. Mol Cancer Ther. 2012 Oct;11(10):2183–2192. doi: 10.1158/1535-7163.MCT-12-0552
   PubMed Web of Science ®Google Scholar
• Schinkel AH. P-Glycoprotein, a gatekeeper in the blood-brain barrier. Adv Drug Delivery Rev. 1999;36(2–3):179–194. doi: 10.1016/S0169-409X(98)00085-4
   PubMed Web of Science ®Google Scholar
• Kim M, Kizilbash SH, Laramy JK, et al. Barriers tor effective drug treatment for brain metastases: a mulltifactorial problem in the delivery of precision medicine. Pharm Res. 2018;35(9):177. doi: 10.1007/s11095-018-2455-9
   PubMed Web of Science ®Google Scholar
• Loganzo F, Tan X, Sung M, et al. Tumor cells chronically treated with a trastuzumab–maytansinoid antibody–drug conjugate develop varied resistance mechanisms but respond to alternate treatments. Mol Cancer Ther. 2015;14(4):952–963. doi: 10.1158/1535-7163.MCT-14-0862
   PubMed Web of Science ®Google Scholar
• Chen R, Hou J, Newman E, et al. CD30 downregulation, MMAE resistance, and MDR1 upregulation are all associated with resistance to brentuximab vedotin. Mol Cancer Ther. 2015;14(6):1376–1384. doi: 10.1158/1535-7163.MCT-15-0036
   PubMed Web of Science ®Google Scholar
• Drappatz J, Brenner A, Wong ET, et al. Phase I study of GRN1005 in recurrent malignant glioma. Clin Cancer Res. 2013 Mar 15;19(6):1567–1576. doi: 10.1158/1078-0432.CCR-12-2481
   PubMed Web of Science ®Google Scholar
• Nounou MI, Adkins CE, Rubinchik S, et al. Anti-cancer antibody trastuzumab-melanotransferrin conjugate (BT2111) for the treatment of metastatic HER2+ breast cancer tumors in the brain: an in-vivo study. Pharm Res. 2016;33(12):2930–2942. doi: 10.1007/s11095-016-2015-0
   PubMed Web of Science ®Google Scholar
• Sarkaria JN, Hu LS, Parney IF, et al. Is the blood–brain barrier really disrupted in all glioblastomas? A critical assessment of existing clinical data. Neuro Oncol. 2017;20(2):184–191. doi: 10.1093/neuonc/nox175
   Web of Science ®Google Scholar
• Coats S, Williams M, Kebble B, et al. Antibody–drug conjugates: future directions in clinical and translational strategies to improve the therapeutic index. Clin Cancer Res. 2019;25(18):5441–5448. doi: 10.1158/1078-0432.CCR-19-0272
   PubMed Web of Science ®Google Scholar
• Amero P, Khatua S, Rodriguez-Aguayo C, et al. Aptamers: novel therapeutics and potential role in Neuro-Oncology. Cancers. 2020;12(10):2889. doi: 10.3390/cancers12102889
   PubMed Web of Science ®Google Scholar
• Nimjee SM, White RR, Becker RC, et al. Aptamers as therapeutics. Annual review of pharmacology and toxicology. Annu Rev Pharmacol Toxicol. 2017;57(1):61–79. doi: 10.1146/annurev-pharmtox-010716-104558
   PubMedGoogle Scholar
• Monaco I, Camorani S, Colecchia D, et al. Aptamer functionalization of nanosystems for glioblastoma targeting through the blood–brain barrier. J Med Chem. 2017;60(10):4510–4516. doi: 10.1021/acs.jmedchem.7b00527
   PubMed Web of Science ®Google Scholar
• Nuzzo S, Brancato V, Affinito A, et al. The role of RNA and DNA Aptamers in glioblastoma diagnosis and therapy: a systematic review of the literature. Cancers. 2020;12(8):2173. doi: 10.3390/cancers12082173
   PubMed Web of Science ®Google Scholar
• Pourgholi F, Hajivalili M, Farhad J-N, et al. Nanoparticles: novel vehicles in treatment of glioblastoma. Biomed Pharmacother. 2016 Feb 01;77:98–107.
   PubMed Web of Science ®Google Scholar
• Whittle JR, Lickliter JD, Gan HK, et al. First in human nanotechnology doxorubicin delivery system to target epidermal growth factor receptors in recurrent glioblastoma. J Clin Neurosci. 2015 Aug 13;22(12):1889–1894. doi: 10.1016/j.jocn.2015.06.005
   PubMed Web of Science ®Google Scholar
• Kouhi A, Pachipulusu V, Kapenstein T, et al. Brain disposition of antibody-based therapeutics: dogma, approaches and perspectives. Int J Mol Sci. 2021 Jun 16;22(12):6442. doi: 10.3390/ijms22126442
   PubMed Web of Science ®Google Scholar
• Kadry H, Noorani B, Cucullo L. A blood–brain barrier overview on structure, function, impairment, and biomarkers of integrity. Fluids Barriers CNS. 2020 Nov 18;17(1):69.
   PubMed Web of Science ®Google Scholar
• Lu CT, Zhao YZ, Wong HL, et al. Current approaches to enhance CNS delivery of drugs across the brain barriers. Int J Nanomed. 2014;9:2241–2257. doi: 10.2147/IJN.S61288
   PubMed Web of Science ®Google Scholar
• Tashima T. Proteolysis-Targeting Chimera (PROTAC) delivery into the brain across the blood-brain barrier. Antibodies. 2023;12(3):43. doi: 10.3390/antib12030043
   Web of Science ®Google Scholar
• Peng SL, Saunders L, Bheddah S, et al. Metastatic melanoma, glioblastoma and high-grade extrapulmonary neuroendocrine carcinomas (NECs) as novel indications for rovalpituzumab tesirine: A delta-like protein 3 (DLL3)-targeted antibody-drug conjugate (ADC). Am Soc Clin Oncol. 2016;34(15_suppl):11611–11611. doi: 10.1200/JCO.2016.34.15_suppl.11611
   Web of Science ®Google Scholar
• Saunders LR, Bankovich AJ, Anderson WC, et al. A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo. Sci, trans med. 2015;7(302):ra302136–ra302136. doi: 10.1126/scitranslmed.aac9459
   Web of Science ®Google Scholar
• Spino M, Kurz SC, Chiriboga L, et al. Cell surface Notch ligand DLL3 is a therapeutic target in isocitrate dehydrogenase–mutant glioma. Clin Cancer Res. 2019;25(4):1261–1271. doi: 10.1158/1078-0432.CCR-18-2312
   PubMed Web of Science ®Google Scholar
• Mansfield AS, Hong DS, Hann CL, et al. A phase I/II study of rovalpituzumab tesirine in delta-like 3-expressing, advanced solid tumors. Am Soc Clin Oncol. 2020;38(15_suppl):3552–3552. doi: 10.1200/JCO.2020.38.15_suppl.3552
   Web of Science ®Google Scholar
• Dufrusine B, Capone E, Ponziani S, et al. Extracellular LGALS3BP: a potential disease marker and actionable target for antibody–drug conjugate therapy in glioblastoma. Molecular Oncology. 2023 May 17;17(8):1460–1473. doi: 10.1002/1878-0261.13453
   PubMed Web of Science ®Google Scholar
• Purcell JW, Tanlimco SG, Hickson J, et al. LRRC15 is a novel mesenchymal protein and stromal target for antibody–drug conjugates. Cancer Res. 2018;78(14):4059–4072. doi: 10.1158/0008-5472.CAN-18-0327
   PubMed Web of Science ®Google Scholar
• Li Y, Si R, Wang J, et al. Discovery of novel antibody-drug conjugates bearing tissue protease specific linker with both anti-angiogenic and strong cytotoxic effects. Bioorg Chem. 2023 Aug;137:106575.
   PubMed Web of Science ®Google Scholar
• London M, Gallo E. Critical role of EphA3 in cancer and current state of EphA3 drug therapeutics. Mol Biol Rep. 2020 Jul;47(7):5523–5533. doi: 10.1007/s11033-020-05571-8
   PubMed Web of Science ®Google Scholar
• Day BW, Stringer BW, Al-Ejeh F, et al. EphA3 maintains tumorigenicity and is a therapeutic target in glioblastoma multiforme. Cancer Cell. 2013;23(2):238–248. doi: 10.1016/j.ccr.2013.01.007
   PubMed Web of Science ®Google Scholar
• Offenhäuser C, Al-Ejeh F, Puttick S, et al. EphA3 pay-loaded antibody therapeutics for the treatment of glioblastoma. Cancers. 2018 Dec 17;10(12):519. doi: 10.3390/cancers10120519
   PubMed Web of Science ®Google Scholar
• Gan H, Cher L, Inglis P, et al. Phase I safety and bioimaging trial of KB004 (ifabotuzumab) in patients with glioblastoma. J Nucl Med. 2020;61(supplement 1):1562–1562.
   Google Scholar
• Rios-Doria J, Harper J, Rothstein R, et al. Antibody–drug conjugates bearing pyrrolobenzodiazepine or tubulysin payloads are immunomodulatory and synergize with multiple immunotherapies. Cancer Res. 2017;77(10):2686–2698. doi: 10.1158/0008-5472.CAN-16-2854
   PubMed Web of Science ®Google Scholar
• Weiss T, Puca E, Silginer M, et al. Immunocytokines are a promising immunotherapeutic approach against glioblastoma. Sci, trans med. 2020 Oct 7;12(564). doi: 10.1126/scitranslmed.abb2311
   Web of Science ®Google Scholar
• Mao Y, Wei D, Fu F, et al. Development of a MMAE-based antibody-drug conjugate targeting B7-H3 for glioblastoma. Eur J Med Chem. 2023 May 20;257:115489.
   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. FBL. 2022 Aug 23;27(8):240.
   Google Scholar
• Yu K, Hu Y, Wu F, et al. Surveying brain tumor heterogeneity by single-cell RNA-sequencing of multi-sector biopsies. Natl Sci Rev. 2020;7(8):1306–1318. doi: 10.1093/nsr/nwaa099
   PubMed Web of Science ®Google Scholar
• McGranahan N, Swanton C. Biological and therapeutic impact of intratumor heterogeneity in cancer evolution. Cancer Cell. 2015 Jan 12;27(1):15–26.
   PubMed Web of Science ®Google Scholar
• Francis JM, Zhang C-Z, Maire CL, et al. EGFR variant heterogeneity in glioblastoma resolved through single-nucleus sequencing. Cancer Discov. 2014;4(8):956–971. doi: 10.1158/2159-8290.CD-13-0879
   PubMed Web of Science ®Google Scholar
• Felsberg J, Hentschel B, Kaulich K, et al. Epidermal growth factor receptor variant III (EGFRvIII) positivity in EGFR-amplified glioblastomas: prognostic role and comparison between primary and recurrent tumors. Clin Cancer Res. 2017;23(22):6846–6855. doi: 10.1158/1078-0432.CCR-17-0890
   PubMed Web of Science ®Google Scholar
• Nathanson DA, Gini B, Mottahedeh J, et al. Targeted therapy resistance mediated by dynamic regulation of extrachromosomal mutant EGFR DNA. Science. 2014;343(6166):72–76. doi: 10.1126/science.1241328
   PubMed Web of Science ®Google Scholar
• Ahluwalia MS, Dimino CR, Mansukhani MM, et al. Effect of therapeutic pressure on stability of EGFR amplification in glioblastoma. J Clin Oncol. 2018;36(15_suppl):2033–2033. doi: 10.1200/JCO.2018.36.15_suppl.2033
   Web of Science ®Google Scholar
• Anderson MG, Falls HD, Mitten MJ, et al. Targeting multiple EGFR-expressing tumors with a highly potent tumor-selective antibody-drug conjugate. Mol Cancer Ther. 2020 Oct;19(10):2117–2125. doi: 10.1158/1535-7163.MCT-20-0149
   PubMed Web of Science ®Google Scholar
• Levengood MR, Zhang X, Hunter JH, et al. Orthogonal cysteine protection enables homogeneous multi‐drug antibody–drug conjugates. Angewandte Chemie. 2017;56(3):733–737. doi: 10.1002/anie.201608292
   Google Scholar
• Bausart M, Préat V, Malfanti A. Immunotherapy for glioblastoma: the promise of combination strategies. J Exp Clin Cancer Res. 2022 Jan 25;41(1):35.
   PubMed Web of Science ®Google Scholar
• Gerber H-P, Sapra P, Loganzo F, et al. Combining antibody–drug conjugates and immune-mediated cancer therapy: what to expect? Biochem Pharmacol. 2016;102:1–6. doi: 10.1016/j.bcp.2015.12.008
   PubMed Web of Science ®Google Scholar
• Griguolo G, Pascual T, Dieci MV, et al. Interaction of host immunity with HER2-targeted treatment and tumor heterogeneity in HER2-positive breast cancer. J Immunother Cancer. 2019;7(1):1–14. doi: 10.1186/s40425-019-0548-6
   PubMedGoogle Scholar
• Khattar M, Traore T, Horton K, et al. Synergy of an anti-HER2 ADC TAK-522 (XMT-1522) in combination with anti-PD1 monoclonal antibody (mAb) in a syngeneic breast cancer model expressing human HER2. Am Assoc Immnol. 2018;200(1_Supplement):.122.29–.122.29. doi: 10.4049/jimmunol.200.Supp.122.29
   Web of Science ®Google Scholar
• Müller P, Kreuzaler M, Khan T, et al. Trastuzumab emtansine (T-DM1) renders HER2+ breast cancer highly susceptible to CTLA-4/PD-1 blockade. Sci, Trans Med. 2015;7(315):ra315188–ra315188. doi: 10.1126/scitranslmed.aac4925
   Web of Science ®Google Scholar
• Reardon DA, Lassman AB, van den Bent M, et al. Efficacy and safety results of ABT-414 in combination with radiation and temozolomide in newly diagnosed glioblastoma. Neuro Oncol. 2016;now257. doi: 10.1093/neuonc/now257
   Google Scholar
• Lassman AB, Gan HK, Roberts-Rapp L, et al. Identifying the correct patient population for depatuxizumab mafodotin (ABT-414): biomarker assays for Epidermal growth factor receptor (EGFR) in patients with glioblastoma. WFNO. 2017 May 4-7;19(suppl_3):iii75–iii75. Zurich2017. doi:10.1093/neuonc/nox036.281
   Google Scholar
• Desjardins A, Chandramohan V, Landi DB, et al. A phase 1 trial of D2C7-it in combination with an Fc-engineered anti-CD40 monoclonal antibody (2141-V11) administered intratumorally via convection-enhanced delivery for adult patients with recurrent malignant glioma (MG). J Clin Oncol. 2022;40(16_suppl):e14015–e14015. doi: 10.1200/JCO.2022.40.16_suppl.e14015
   Web of Science ®Google Scholar
• Ileana Dumbrava E, Meric-Bernstam F, Yap TA. Challenges with biomarkers in cancer drug discovery and development. Expert opinion on drug discovery. Expert Opin Drug Discov. 2018;13(8):685–690. doi: 10.1080/17460441.2018.1479740
   PubMed Web of Science ®Google Scholar
• Linehan AS, Fitzpatrick OM, Morris PG. Profile of trastuzumab deruxtecan in the management of patients with HER2-positive unresectable or metastatic breast Cancer: an evidence-based review. Breast Cancer: Target Therapy. 2021;13:151. doi: 10.2147/BCTT.S245024
   PubMed Web of Science ®Google Scholar
• Tsurutani J, Iwata H, Krop I, et al. Targeting HER2 with trastuzumab deruxtecan: a dose-expansion, phase I study in multiple advanced solid tumors. Cancer Discov. 2020;10(5):688–701. doi: 10.1158/2159-8290.CD-19-1014
   PubMed Web of Science ®Google Scholar
• Janes PW, Vail ME, Gan HK, et al. Antibody targeting of Eph receptors in Cancer. Pharmaceuticals. 2020;13(5):88. doi: 10.3390/ph13050088
   Web of Science ®Google Scholar
• Lassman A, Roberts-Rapp L, He L, et al. PATH-29. Molecular determinants associated with response and resistance to depatuxizumab mafodotin (abt-414) in patients with recurrent glioblastoma. Neuro Oncol. 2017;19(suppl_6):vi176–vi177. doi: 10.1093/neuonc/nox168.719
   Google Scholar
• Leu AJ, Berk DA, Lymboussaki A, et al. Absence of functional lymphatics within a murine sarcoma: a molecular and functional evaluation. Cancer Res. 2000;60(16):4324–4327.
   PubMed Web of Science ®Google Scholar
• Munson JM, Shieh AC. Interstitial fluid flow in cancer: implications for disease progression and treatment. Cancer Manag Res. 2014;6:317. doi: 10.2147/CMAR.S65444
   PubMed Web of Science ®Google Scholar
• Harder BG, Blomquist MR, Wang J, et al. Developments in blood-brain barrier penetrance and drug repurposing for improved treatment of glioblastoma. Front Oncol. 2018;8: doi: 10.3389/fonc.2018.00462
   PubMed Web of Science ®Google Scholar
• Gan H, Seow A, Lau E, et al. ACTR-55. Tumour volume as a predictor of response to Ant-EGFR ADC ABT-414. Neuro Oncol. 2018;20(suppl_6):vi24–vi24. doi: 10.1093/neuonc/noy148.087
   Google Scholar
• Trédan O, Galmarini CM, Patel K, et al. Drug resistance and the solid tumor microenvironment. JNCI. 2007;99(19):1441–1454. doi: 10.1093/jnci/djm135
   PubMed Web of Science ®Google Scholar
• Böckelmann LC, Schumacher U. Targeting tumor interstitial fluid pressure: will it yield novel successful therapies for solid tumors? Expert opinion on therapeutic targets. Expert Opin Ther Targets. 2019;23(12):1005–1014. doi: 10.1080/14728222.2019.1702974
   PubMed Web of Science ®Google Scholar
• Heldin C-H, Rubin K, Pietras K, et al. High interstitial fluid pressure—an obstacle in cancer therapy. Nat Rev Cancer. 2004;4(10):806–813. doi: 10.1038/nrc1456
   PubMed Web of Science ®Google Scholar
• Mellinghoff IK, van den Bent MJ, Blumenthal DT, et al. Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma. N Engl J Med. 2023;389(7):589–601. doi: 10.1056/NEJMoa2304194
   PubMed Web of Science ®Google Scholar
• Mellinghoff IK, Penas-Prado M, Peters KB, et al. Vorasidenib, a dual inhibitor of mutant IDH1/2, in recurrent or progressive glioma; results of a first-in-human phase I trial. Clin Cancer Res. 2021 Aug 15;27(16):4491–4499. doi: 10.1158/1078-0432.CCR-21-0611
   PubMed Web of Science ®Google Scholar
• Perreault S, van Tilburg CM, Geoerger B, et al. Efficacy and safety of larotrectinib in adult and pediatric patients with tropomyosin receptor kinase (TRK) fusion-positive primary central nervous system tumors. J Clin Oncol. 2021;39(15_suppl):2002–2002. doi: 10.1200/JCO.2021.39.15_suppl.2002
   Web of Science ®Google Scholar
• Aldape K, Brindle KM, Chesler L, et al. Challenges to curing primary brain tumours. Nat Rev Clin Oncol. 2019 Feb 07;16(8):509–520. doi: 10.1038/s41571-019-0177-5
   PubMed Web of Science ®Google Scholar