Induced Pluripotent Stem
Cells Provide an Unlimited T-cell Source for CAR-T cell Development and
A Potential Source for Off-the-shelf Products
Muhammad Sadeqi Nezhad 1,2, Meghdad Abdollahpour-Alitappeh 3 , Behzad Rezaei 4 ,
Alexander Seifalian 5*
1 Department of Clinical Laboratory Science, Azad University, 2 Blood Transfusion Research Center,
High Institute for Research and Education in Transfusion Medicine, Gorgan, Iran, 3 Cellular and
Molecular Biology Research Center, 4 Department of Surgery, Larestan University of Medical
Sciences, Larestan, Iran, 5 Nanotechnology & Regenerative Medicine Commercialization Centre (Ltd),
London BioScience Innovation Centre, London, United Kingdom
Alexander Marcus Seifalian (ORCID: 0000-0002-8334-9376)
Director/Professor of Nanotechnology & Regenerative Medicine
Abstract
CAR-T cell therapy has been increasingly conducted for cancer patients in clinical settings. Progress in this therapeutic approach is hampered by the lack of a solid manufacturing process, T lymphocytes, and tumor-specific antigens. T-cell source used in CAR-T cell therapy is predominantly derived from the patient’s own T lymphocytes, which makes this approach impracticable to patients with progressive diseases and T leukemia. Autologous CAR-T cell generation is time-consuming due to lack of readily available T lymphocytes and is not applicable for third-party patients. Pluripotent stem cells, such as human induced pluripotent stem cells (hiPSCs), could provide
an unlimited T-cell source for CAR-T cell development. iPSC-derived T cells would be a promising infinite T-cell source and are phenotypically defined, expandable and functional as physiological T cells. iPSC-derived T cells provide a feasible T-cell source for the development of off-the-shelf T cells and CAR-T cells. The combination of iPSC and CAR-Technologies provides an extraordinary opportunity to oncology and greatly facilitates cell-based therapy for cancer patients. T-iPSCs in combination with CAR is in early stage of development and the pre-clinical and clinical studies concerning the combination of these novel technologies are not sufficient. This article critically reviews the progress in iPSC-derived T cell development and provides a roadmap for development of CAR iPSC-derived T cells and off-the-shelf T-iPSCs.
Keywords: CAR-T cell; iPSC; T cell; iPSC-derived T cell; tumor cell; therapeutic; off-the-shelf
1- PBMCs are a promising somatic cell source for iPSC-derived T cell generation
2- iPSC-derived T cells provide an unlimited T cell source for CAR-T cell development
3- iPSC-derived T cells can be engineered with artificial receptors, CARs, and showed therapeutic potential
4- The combination of iPSC and CAR technologies is in preliminary stage of investigation and so many questions remained with no constructive answers
Running title: Application of iPSC-derived T cell for CAR-T development