Abstract Number: OC 26.2
Meeting: ISTH 2022 Congress
Background: Platelet products are provided from blood banks which collect blood from healthy donors. However, approximately 5% of platelet transfusion patients are complicated with alloimmune platelet transfusion refractoriness (allo-PTR) due to alloantibodies against class I human leukocyte antigens (HLA-I) or human platelet antigens (HPA). In these cases, platelets from compatible donors are transfused, but for patients with rare HLA-I or HPA, donors are difficult to find. Aiming to ultimately solve this issue, we had developed ex vivo production system of iPSC-derived platelet products (iPSC-PLTs).
Aims: We aimed to assess the safety and efficacy of autologous iPSC-PLTs in an aplastic anemia patient with allo-PTR due to rare HPA-1 mismatch in Japan.
Methods: The iPSC-PLTs were produced from megakaryocyte cell lines (imMKCLs) established from patient iPSCs using turbulent flow bioreactors and new drugs. In preclinical studies, iPSC-PLTs were confirmed for quality, safety, and efficacy, including hemostasis in animal models. We then performed the first-in-human clinical trial of iPSC-PLTs as a phase I study of autologous transfusion. Three escalating doses of 0.1 x 1011, 0.3 x 1011 and 1 x 1011 iPSC-PLTs were sequentially administered.
Results: The primary endpoint was safety, and no significant adverse event was observed over one year. The secondary endpoint of corrected count increment showed no significant change in all dose cohorts. Circulation of larger size possibly iPSC-PLTs was observed, but there was also a slight increase in d-dimer.
Conclusion(s): This first-in-human clinical trial provides extensive resource of successful GMP-based production of iPSC-PLTs with no significant adverse event profile, as well as issues that needs to be overcome, thereby marking a first benchmark in realizing iPSC-PLTs as a clinical measure. (Funded by the Japan Agency for Medical Research and Development; This trial was registered at Japan Registry of Clinical Trials as jRCTa050190117)
To cite this abstract in AMA style:Sugimoto N, kanda J, Nakamura S, Kitano T, Shimizu S, Shigemasa A, Hirai H, Minami M, Tada H, Momose D, Koh K, Nogawa M, Watanabe N, Handa M, Sawaguchi A, Tanaka M, Hayashi T, Tani Y, Takaori-Kondo A, Eto K. A dose-escalation phase 1 clinical trial of autologous iPSC-derived platelets (iPLAT1) [abstract]. https://abstracts.isth.org/abstract/a-dose-escalation-phase-1-clinical-trial-of-autologous-ipsc-derived-platelets-iplat1/. Accessed September 26, 2022.
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