Accelerating the development of genetically engineered cellular therapies: a framework for extrapolating data across related products.

Significant advancements have been made in the field of cellular therapy as anti-cancer treatments, with the approval of chimeric antigen receptor (CAR)-T cell therapies and the development of other genetically engineered cellular therapies. CAR-T cell therapies have demonstrated remarkable clinical outcomes in various hematological malignancies, establishing their potential to change the current cancer treatment paradigm. Due to the increasing importance of genetically engineered cellular therapies in the oncology treatment landscape, implementing strategies to expedite development and evidence generation for the next generation of cellular therapy products can have a positive impact on patients. We outline a risk-based methodology and assessment aid for the data extrapolation approach across related genetically engineered cellular therapy products. This systematic data extrapolation approach has applicability beyond CAR-T cells and can influence clinical development strategies for a variety of immune therapies such as T cell receptor (TCR) or genetically engineered and other cell-based therapies (e.g., tumor infiltrating lymphocytes, natural killer cells and macrophages). By analyzing commonalities in manufacturing processes, clinical trial designs, and regulatory considerations, key learnings were identified. These insights support optimization of the development and regulatory approval of novel cellular therapies. The field of cellular therapy holds immense promise in safely and effectively treating cancer. The ability to extrapolate data across related products presents opportunities to streamline the development process and accelerate the delivery of novel therapies to patients.

Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.

Declaration of competing interest M.K. holds IP related to cell therapy, assigned to the University of Pennsylvania and licensed to Novartis, board memberships with IMVinc, Nanocell therapeutics, and is on scientific advisory boards for AdicetBio, Annoca AG, cTRL-therapeutics, Cue Biopharma, Lykan Bioscience, Senti Biosciences, Vittoria Therapeutics. J.J is an employee of Kite, A Gilead Company. J.Y. is an employee of Janssen R&D, LLC. M.F is an employee of Novartis. S.G. is an employee of Allogene Therapeutics. C.G. is an employee of GSK. P.J.H. is a Scientific Advisor or Advisory Board for Cellenkos, Cellevolve, Discovery Life Sciences, Microfluidx, Autolomous, Capsida and is co-founder, board of directors of Mana Therapeutics. J.H. is an employee of Merck & Co. Inc. W. L. is an employee of Lyell Immunopharma. L.P. is an employee of the Canadian Cancer Trials Group and past employee of GSK, and holds shares in GSK. S.P.T reports that Moffitt Cancer Center has licensed Intellectual Property (IP) related to the proliferation and expansion of tumor infiltrating lymphocytes (TILs) to Iovance Biotherapeutics. Moffitt has also licensed IP to Tuhura Biopharma. S.P.T. is an inventor on such Intellectual Property. SPT has received consulting fees from Seagen Inc., Morphogenesis Inc., and KSQ Therapeutics. M.V. is an employee of Genentech, Inc. J.V. is an employee of A2 Biotherapeutics, Inc. S.W. is an employee of Bristol Myers Squibb. All other authors report no potential conflicts.