Biomedical Science Letters (대한의생명과학회지)

The Korean Society for Biomedical Laboratory Sciences (대한의생명과학회)
권호 표지
DOI QR코드

DOI QR Code

Market Trend and Current Status of the Research and Development of Antibody-Drug Conjugates

  • Kwon, Sun-Il (Department of Biomedical Laboratory Science, Deagu Health Science University)
  • Received : 2021.08.18
  • Accepted : 2021.09.27
  • Published : 2021.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Antibody-drug conjugates (ADCs) are drawing much interest due to its great potential to be one of the important options in cancer treatments. ADCs are acting like a magic bullet which delivers cytotoxic drugs specifically to cancerous cells throughout the body, thus attacks these cells, while not harming healthy cells. ADCs are complex molecules that are composed of an antibody having targeting capability and linked-payload or cytotoxic drug killing cancerous cells. The key factors of the success in the development of ADC are selection of appropriate antibody, cytotoxic payload and linker for conjugation. Recently there was considerable progress in ADCs development, and a large number of ADCs gained US FDA approval. About 80 new ADCs are under active clinical studies. In this review we present a brief introduction of the US-FDA approved ADCs and global situation in the clinical studies of ADC pipelines. We address an overview on each component of an ADC design such as target antigens, payloads, linkers, conjugation methods, drug antibody ratio. In addition, we discuss on the trend of ADC market where global big pharmas and domestic biopharmaceutical companies are competing to develop safer and more effective ADCs.

Keywords

References

  1. Bae JJ. The history of Artillery is repeated. ADC, The anticancer drugs loaded with warheads. MediGate News. 2019. 4. 12.
  2. Barginear MF, John V, Budman DR. Trastuzumab-DM1: a clinical update of the novel antibody-drug conjugate for HER2-overexpressing breast cancer. Mol Med. 2013. 18: 1473-1479. https://doi.org/10.2119/molmed.2012.00302
  3. Biochempeg, Worldwide PEG Supplier home page. 11 FDA approved ADC, An overview. (https://www.biochempeg.com/article/74.html) as of 2021. 8. 15.
  4. Choi SJ. The reason why LegoChemBio is a must-go-restaurant of Bio Industry. PharmNews. 2021. 3. 22.
  5. ClinicalTrials.com. https://www.clinicaltrials.gov/ as of 2021. 8. 15.
  6. Damelin M, Zhong W, Myers J, Sapra P. Evolving Strategies for Target Selection for Antibody-Drug Conjugates. Pharm Res. 2015. 32: 3494-3507. https://doi.org/10.1007/s11095-015-1624-3
  7. Dean AQ, Luo S, Twomey JD, Zhang B. Targeting cancer with antibody-drug conjugates: Promises and challenges. MAbs. 2021. 13: e1951427(23 pages).
  8. Deeks ED. Polatuzumab Vedotin: First Global Approval. Drugs. 2019. 79: 1467-1475. https://doi.org/10.1007/s40265-019-01175-0
  9. Evaluate pharma 2020. https://www.evaluate.com/thought-leadership/vantage/evaluate-vantage-2021-preview.
  10. Figueroa-Vazquez V, Ko J, Breunig C, et al. HDP-101, an Anti-BCMA Antibody-Drug Conjugate, Safely Delivers Amanitin to Induce Cell Death in Proliferating and Resting Multiple Myeloma Cells. Mol Cancer Ther. 2021. 20: 367-378. https://doi.org/10.1158/1535-7163.MCT-20-0287
  11. Frega G, Wu Q, Le Naour J, et al. Trial Watch: experimental TLR7/TLR8 agonists for oncological indications. Oncoimmunology. 2020. 9: 1796002. https://doi.org/10.1080/2162402X.2020.1796002
  12. Goldenberg DM, Sharkey RM. Sacituzumab govitecan, a novel, third-generation, antibody-drug conjugate (ADC) for cancer therapy. Expert Opin Biol Ther. 2020. 20: 871-885. https://doi.org/10.1080/14712598.2020.1757067
  13. Ha SJ. Alteogen, developing ovarian cancer drug, ALT-Q5 with ADC biobetter technology. Health In News. 2021. 7. 6.
  14. Hammood M, Craig AW, Leyton JV. Impact of Endocytosis Mechanisms for the Receptors Targeted by the Currently Approved Antibody-Drug Conjugates (ADCs)-A Necessity for Future ADC Research and Development. Pharmaceuticals (Basel). 2021. 14: 674. https://doi.org/10.3390/ph14070674
  15. Hasan M, Alam S, Poddar SK. Antibody-Drug Conjugates: A Review on the Epitome of Targeted Anti-Cancer Therapy. Curr Clin Pharmacol. 2018. 13: 236-251. https://doi.org/10.2174/1574884712666180802095521
  16. Hong ST. Intocell, ADC, Drug linked with linker technology, kills cancer cells selectively. HelloDD. 2020. 12. 28.
  17. Hong YD, Kang KG, Jung JY, Ha SJ, Lim KS. Antibody-drug conjugates: Development and advances. Korean Soc for Biotech & Bioeng J. 2021. 36: 87-98.
  18. Hwang JJ. K-bio develops Drug + antibody, the next generation new drug ADC. Economic Review. 2021. 7. 30.
  19. Jabbour E, Paul S, Kantarjian H. The clinical development of antibody-drug conjugates - lessons from leukaemia. Nat Rev Clin Oncol. 2021. 18: 418-433. https://doi.org/10.1038/s41571-021-00484-2
  20. Jang YS. Gilead tries to merge US Immunomedics at 230 billion dollars. ChosunBiz. 2020. 9. 13.
  21. Jain N, Smith SW, Ghone S, Tomczuk B. Current ADC Linker Chemistry. Pharm Res. 2015. 32: 3526-3540. https://doi.org/10.1007/s11095-015-1657-7
  22. Joubert N, Beck A, Dumontet C, Denevault-Sabourin C. Antibody-Drug Conjugates: The Last Decade. Pharmaceuticals (Basel). 2020. 13: 245. https://doi.org/10.3390/ph13090245
  23. Jun SM. antibody drug market, Watch immunocytokine-ADC therapy. selective effect on cancer cells. Yakup.com. 2020. 10. 21.
  24. 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. 26: 925-932. https://doi.org/10.1038/nbt.1480
  25. Katz J, Janik JE, Younes A. Brentuximab Vedotin (SGN-35). Clin Cancer Res. 2011. 17: 6428-6436. https://doi.org/10.1158/1078-0432.ccr-11-0488
  26. Keam SJ. Trastuzumab Deruxtecan: First Approval. Drugs. 2020. 80: 501-508. https://doi.org/10.1007/s40265-020-01281-4
  27. Kim MK. Trends for Antibody-drug Conjugates for Therapy). Biochemistry and Molecular Biology News. 2011. 31: 43-52.
  28. Kim MK. The key of next generation ADC platform is linker. The linker determines efficacy and toxicity. DailyPharm. 2018. 9. 18.
  29. Kim SM. ABLBio improved half-life and toxicity with ADC plarform NTERM®. BioSpectator. 2021. 4. 48.
  30. KoBIA (Korea Biomedicine Industry Association). Global biopharmaceutical market trend. Biopharmaceutical industry. 2021. as of 2021.8.8https://www.kobia.kr/sub01/sub01_2.php
  31. Kostova V, Desos P, Starck JB, Kotschy A. The Chemistry Behind ADCs. Pharmaceuticals (Basel). 2021. 14: 442. https://doi.org/10.3390/ph14050442
  32. Lee HK. MSD reinforces to collaborate with Seattle Genetics on anticancer drugs. Medical News. 2020. 9. 15.
  33. Lee YJ, Toward the unicons.. Selection of the first baby 40 unicons. Doctor's News. 2020. 6. 30.
  34. Li Z, Li Y, Chang HP, Chang HY, Guo L, Shah DK. Effect of Size on Solid Tumor Disposition of Protein Therapeutics. Drug Metab Dispos. 2019. 47: 1136-1145. https://doi.org/10.1124/dmd.119.087809
  35. Markham A. Belantamab Mafodotin: First Approval. Drugs. 2020. 80: 1607-1613. https://doi.org/10.1007/s40265-020-01404-x
  36. McGregor BA, Sonpavde G. Enfortumab Vedotin, a fully human monoclonal antibody against Nectin 4 conjugated to mono-methyl auristatin E for metastatic urothelial Carcinoma. Expert Opin Investig Drugs. 2019. 28: 821-826. https://doi.org/10.1080/13543784.2019.1667332
  37. Mullard A. FDA approves ADC Therapeutics' loncastuximab tesirine, ushering in a new cytotoxic payload. Nat Rev Drug Discov. 2021. 20: 414.
  38. Ogitani Y, Aida T, Hagihara K, et al. DS-8201a, A Novel HER2-Targeting ADC with a Novel DNA Topoisomerase I Inhibitor, Demonstrates a Promising Antitumor Efficacy with Differentiation from T-DM1. Clin Cancer Res. 2016. 22: 5097-5108. https://doi.org/10.1158/1078-0432.ccr-15-2822
  39. Park BJ. ADC. the war searching optimum combination of antibody-linker-payload. Health Care Herb Hit News. 2021. 7. 27.
  40. Seo YS. Celltrion invests 47 million dollars to Iksuda Therapeutics to have ADC. BioSpectator. 2021. 6. 7.
  41. Shin SH, Park MH, Byeon JJ, et al. Market Trends of antibody-drug conjugate and its new platform technologies. Yakhak Hoeji, 2018. 62: 158-170. https://doi.org/10.17480/psk.2018.62.3.158
  42. Su D, Zhang D. Linker Design Impacts Antibody-Drug Conjugate Pharmacokinetics and Efficacy via Modulating the Stability and Payload Release Efficiency. Front Pharmacol. 2021. 12: 687926. https://doi.org/10.3389/fphar.2021.687926
  43. Tai YT, Mayes PA, Acharya C, et al. Novel anti-B-cell maturation antigen antibody-drug conjugate (GSK2857916) selectively induces killing of multiple myeloma. Blood. 2014. 123: 3128-3138. https://doi.org/10.1182/blood-2013-10-535088
  44. Urquhart L. Market watch, Top drugs and companies by sales in 2017. Nature Reviews Drug Discovery. 2018. 17: 232. https://doi.org/10.1038/nrd.2018.42
  45. Yoo JH. The war against cancer. ADC (antibody-drug conjugate) is coming. Chosun Daily. 2020. 9. 24.
  46. Zhang X, Liu X, Zhou D, Zheng G. Targeting anti-apoptotic BCL2 family proteins for cancer treatment. Future Med Chem. 2020. 12: 563-565.
  47. Zhou Q. Site-Specific Antibody Conjugation for ADC and Beyond.