International Journal of Stem Cells

  • 제16권1호
  • /
  • Pages.16-26
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  • 2023
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  • 2005-3606(pISSN)
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  • 2005-5447(eISSN)
한국줄기세포학회 (Korean Society for Stem Cell Research)
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Establishing Rationale for the Clinical Development of Cell Therapy Products: Consensus between Risk and Benefit

  • Seunghoon Han (Department of Pharmacology, College of Medicine, The Catholic University of Korea) ;
  • Hyeon Woo Yim (Department of Preventive Medicine, College of Medicine, The Catholic University of Korea) ;
  • Hyunsuk Jeong (Department of Preventive Medicine, College of Medicine, The Catholic University of Korea) ;
  • Suein Choi (Department of Pharmacology, College of Medicine, The Catholic University of Korea) ;
  • Sungpil Han (Department of Pharmacology, College of Medicine, The Catholic University of Korea)
  • 투고 : 2021.10.17
  • 심사 : 2022.03.18
  • 발행 : 2023.02.28
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초록

Despite long-term research achievements, the development of cell therapy (CT) products remains challenging. This is because the risks experienced by the subject and therapeutic effects in the clinical trial stage are unclear due to the various uncertainties of CT when administered to humans. Nevertheless, as autologous cell products for systemic administration have recently been approved for marketing, CT product development is accelerating, particularly in the field of unmet medical needs. The human experience of CT remains insufficient compared with other classes of pharmaceuticals, while there are countless products for clinical development. Therefore, for many sponsors, understanding the rationale of human application of an investigational product based on the consensus and improving the ability to apply it appropriately for CT are necessary. Thus, defining the level of evidence for safety and efficacy fundamentally required for initiating the clinical development and preparing it using a reliable method for CT. Furthermore, the expertise should be strengthened in the design of the first-in-human trial, such as the starting dose and dose-escalation plan, based on a sufficiently acceptable rationale. Cultivating development professionals with these skills will increase the opportunity for more candidates to enter the clinical development phase.

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과제정보

This research was supported by a grant (18172MFDS182) from the Ministry of Food & Drug Safety in 2018.

참고문헌

  1. Picanco-Castro V, Goncalves Pereira C, Swiech K, Ribeiro Malmegrim KC, Tadeu Covas D, Silveira Porto G. Emerging CAR T cell therapies: clinical landscape and patent technological routes. Hum Vaccin Immunother 2020;16:1424-1433
  2. Laurencin CT, McClinton A. Regenerative cell-based therapies: cutting edge, bleeding edge, and off the edge. Regen Eng Transl Med 2020;6:78-89
  3. Peng B, Ming Y, Yang C. Regulatory B cells: the cutting edge of immune tolerance in kidney transplantation. Cell Death Dis 2018;9:109
  4. Watanabe Y, Tsuchiya A, Terai S. The development of mesenchymal stem cell therapy in the present, and the perspective of cell-free therapy in the future. Clin Mol Hepatol 2021;27:70-80
  5. Moll G, Ankrum JA, Kamhieh-Milz J, Bieback K, Ringden O, Volk HD, Geissler S, Reinke P. Intravascular mesenchymal stromal/stem cell therapy product diversification: time for new clinical guidelines. Trends Mol Med 2019;25:149-163
  6. Golchin A, Farahany TZ. Biological products: cellular therapy and FDA approved products. Stem Cell Rev Rep 2019;15:166-175
  7. Shukla V, Seoane-Vazquez E, Fawaz S, Brown L, Rodriguez- Monguio R. The landscape of cellular and gene therapy products: authorization, discontinuations, and cost. Hum Gene Ther Clin Dev 2019;30:102-113
  8. Xu J, Sim JW. Characteristics of corporate R&D investment in emerging markets: evidence from manufacturing industry in China and South Korea. Sustainability 2018;10:3002
  9. Bas TG, Oliu Castillo C. Biosimilars in developed and developing East and Southeast Asian countries: Japan, South Korea, and Malaysia-overview, evolution, and regulations assessment. Biomed Res Int 2016;2016:5910403
  10. Mendicino M, Fan Y, Griffin D, Gunter KC, Nichols K. Current state of U.S. Food and Drug Administration regulation for cellular and gene therapy products: potential cures on the horizon. Cytotherapy 2019;21:699-724
  11. Herberts CA, Kwa MS, Hermsen HP. Risk factors in the development of stem cell therapy. J Transl Med 2011;9:29
  12. Izeta A, Herrera C, Mata R, Astori G, Giordano R, Hernandez C, Leyva L, Arias S, Oyonarte S, Carmona G, Cuende N. Cell-based product classification procedure: what can be done differently to improve decisions on borderline products? Cytotherapy 2016;18:809-815
  13. Therapeutic Goods Administration, Department of Health, Australian Government. Intended use: interpretation of homologous use Australian Regulatory Guidelines for Biologicals (ARGB). Version 1.0. Woden: Commonwealth of Australia; 2018.
  14. Schmidt C. FDA approves first cell therapy for wrinkle-free visage. Nat Biotechnol 2011;29:674-675
  15. Dunkin BS, Lattermann C. New and emerging techniques in cartilage repair: MACI. Oper Tech Sports Med 2013;21:100-107
  16. Falanga V, Faria K, Bollenbach T. Bioengineered skin constructs. In: Lanza R, Langer R, Vacanti J, editor. Principles of Tissue Engineering. 4th ed. London: Academic Press; 2014. 1619-1643
  17. Bach PB, Giralt SA, Saltz LB. FDA approval of tisagenlecleucel: promise and complexities of a $475 000 cancer drug. JAMA 2017;318:1861-1862
  18. Ali S, Kjeken R, Niederlaender C, Markey G, Saunders TS, Opsata M, Moltu K, Bremnes B, Gronevik E, Muusse M, Hakonsen GD, Skibeli V, Kalland ME, Wang I, Buajordet I, Urbaniak A, Johnston J, Rantell K, Kerwash E, Schuessler-Lenz M, Salmonson T, Bergh J, Gisselbrecht C, Tzogani K, Papadouli I, Pignatti F. The European Medicines Agency review of kymriah (Tisagenlecleucel) for the treatment of acute lymphoblastic leukemia and diffuse large B-Cell lymphoma. Oncologist 2020;25:e321-e327
  19. Patel S, Burga RA, Powell AB, Chorvinsky EA, Hoq N, McCormack SE, Van Pelt SN, Hanley PJ, Cruz CRY. Beyond CAR T cells: other cell-based immunotherapeutic strategies against cancer. Front Oncol 2019;9:196
  20. Upadhaya S, Yu JX, Shah M, Correa D, Partridge T, Campbell J. The clinical pipeline for cancer cell therapies. Nat Rev Drug Discov 2021;20:503-504
  21. Roselli E, Faramand R, Davila ML. Insight into next-generation CAR therapeutics: designing CAR T cells to improve clinical outcomes. J Clin Invest 2021;131:e142030
  22. Jo Y, Ali LA, Shim JA, Lee BH, Hong C. Innovative CAR-T cell therapy for solid tumor; current duel between CAR-T spear and tumor shield. Cancers (Basel) 2020;12:2087
  23. Hou B, Tang Y, Li W, Zeng Q, Chang D. Efficiency of CAR-T therapy for treatment of solid tumor in clinical trials: a meta-analysis. Dis Markers 2019;2019:3425291
  24. Townsend MH, Bennion K, Robison RA, O'Neill KL. Paving the way towards universal treatment with allogenic T cells. Immunol Res 2020;68:63-70
  25. Alnaggar M, Xu Y, Li J, He J, Chen J, Li M, Wu Q, Lin L, Liang Y, Wang X, Li J, Hu Y, Chen Y, Xu K, Wu Y, Yin Z. Allogenic Vγ9Vδ2 T cell as new potential immunotherapy drug for solid tumor: a case study for cholangiocarcinoma. J Immunother Cancer 2019;7:36
  26. Deinsberger J, Reisinger D, Weber B. Global trends in clinical trials involving pluripotent stem cells: a systematic multi-database analysis. NPJ Regen Med 2020;5:15
  27. Borlongan CV. Concise review: stem cell therapy for stroke patients: are we there yet? Stem Cells Transl Med 2019;8:983-988
  28. Kawabori M, Shichinohe H, Kuroda S, Houkin K. Clinical trials of stem cell therapy for cerebral ischemic stroke. Int J Mol Sci 2020;21:7380
  29. Lalu MM, Mazzarello S, Zlepnig J, Dong YYR, Montroy J, McIntyre L, Devereaux PJ, Stewart DJ, David Mazer C, Barron CC, McIsaac DI, Fergusson DA. Safety and efficacy of adult stem cell therapy for acute myocardial infarction and ischemic heart failure (SafeCell Heart): a systematic review and meta-analysis. Stem Cells Transl Med 2018;7:857-866
  30. Barker RA, Carpenter MK, Forbes S, Goldman SA, Jamieson C, Murry CE, Takahashi J, Weir G. The challenges of first-in-human stem cell clinical trials: what does this mean for ethics and institutional review boards? Stem Cell Reports 2018;10:1429-1431
  31. Center for Biologics Evaluation and Research, US FDA. Considerations for the design of early-phase clinical trials of cellular and gene therapy products; guidance for industry. Silver Spring: FDA; 2015.
  32. Center for Biologics Evaluation and Research, US FDA. Guidance for FDA reviewers and sponsors: content and review of chemistry, manufacturing, and control (CMC) information for human somatic cell therapy investigational new drug applications (INDs). Rockville: FDA; 2015.
  33. Geigert J. An effective CMC strategy is possible. In: Geigert J, editor. The challenge of CMC regulatory compliance for biopharmaceuticals. Cham: Springer; 2019. 53-87
  34. Andrade EL, Bento AF, Cavalli J, Oliveira SK, Schwanke RC, Siqueira JM, Freitas CS, Marcon R, Calixto JB. Non-clinical studies in the process of new drug development - Part II: good laboratory practice, metabolism, pharmacokinetics, safety and dose translation to clinical studies. Braz J Med Biol Res 2016;49:e5646
  35. Steinmetz KL, Spack EG. The basics of preclinical drug development for neurodegenerative disease indications. BMC Neurol 2009;9(Suppl 1):S2
  36. Senderowicz AM. Information needed to conduct first-inhuman oncology trials in the United States: a view from a former FDA medical reviewer. Clin Cancer Res 2010;16:1719-1725
  37. Mager DE, Woo S, Jusko WJ. Scaling pharmacodynamics from in vitro and preclinical animal studies to humans. Drug Metab Pharmacokinet 2009;24:16-24
  38. Lee W, Cai Y, Lim TP, Teo J, Chua SC, Kwa AL. In vitro pharmacodynamics and PK/PD in animals. Adv Exp Med Biol 2019;1145:105-116
  39. Marx U, Akabane T, Andersson TB, Baker E, Beilmann M, Beken S, Brendler-Schwaab S, Cirit M, David R, Dehne EM, Durieux I, Ewart L, Fitzpatrick SC, Frey O, Fuchs F, Griffith LG, Hamilton GA, Hartung T, Hoeng J, Hogberg H, Hughes DJ, Ingber DE, Iskandar A, Kanamori T, Kojima H, Kuehnl J, Leist M, Li B, Loskill P, Mendrick DL, Neumann T, Pallocca G, Rusyn I, Smirnova L, Steger-Hartmann T, Tagle DA, Tonevitsky A, Tsyb S, Trapecar M, Van de Water B, Van den Eijnden-van Raaij J, Vulto P, Watanabe K, Wolf A, Zhou X, Roth A. Biology-inspired microphysiological systems to advance patient benefit and animal welfare in drug development. ALTEX 2020;37:365-394
  40. Kopec AK, Yokokawa R, Khan N, Horii I, Finley JE, Bono CP, Donovan C, Roy J, Harney J, Burdick AD, Jessen B, Lu S, Collinge M, Sadeghian RB, Derzi M, Tomlinson L, Burkhardt JE. Microphysiological systems in early stage drug development: perspectives on current applications and future impact. J Toxicol Sci 2021;46:99-114
  41. ICH Guideline M3 (R2) on Non-clinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals [Internet]. London: European Medicines Agency; 2009 Dec [cited 2019 Mar 24]. Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/ich-guideline-m3r2-non-clinical-safety-studies-conduct-human-clinical-trials-marketing-authorisation_en.pdf.
  42. Settiagounder N. Histopathology evaluation and peer review for nonclinical studies: raw data compliance to GLP quality systems. J Regul Sci 2017;5:45-55
  43. Food and Drug Administration. Summary basis for regulatory action for idecabtagene vicleucel. Silver Spring: FDA; 2021.
  44. European Medicines Agency. Assessment report for Alofisel. London: European Medicines Agency; 2017.
  45. European Medicines Agency. Assessment report for Yescarta. London: European Medicines Agency; 2018.
  46. Food and Drug Administration. Draft Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of Cellular and Gene Therapy Products; Availability. Rockville: FDA; 2013.
  47. Food and Drug Administration. Chemistry, manufacturing, and control (CMC) information for human gene therapy investigational new drug applications (INDs). Rockville: FDA; 2020.