Toward the development of true “off‐the‐shelf” synthetic T‐cell immunotherapy

Abstract

Recent outstanding clinical results produced by engineered T cells, including chimeric antigen receptors, have already facilitated further research that broadens their applicability. One such direction is to explore new T cell sources for allogeneic “off‐the‐shelf” adoptive immunotherapy. Human pluripotent stem cells could serve as an alternative cell source for this purpose due to their unique features of infinite propagation ability and pluripotency. Here, we describe the current state of engineered T cell transfer with the focus on cell manufacturing processes and the potentials and challenges of induced pluripotent stem cell‐derived T cells as a starting material to construct off‐the‐shelf T‐cell banks.

Recent Progress of Stem Cell Therapy in Cancer Treatment: Molecular Mechanisms and Potential Applications

“…In addition, in vivo anti-tumor activity of these CAR immune cells is often limited due to their rapid differentiation into short-lived effector cells [101]. Therefore, there are requirements for the generation of CAR cells from other sources, which enables the expansion of this immunotherapy to a larger number of patients [9,102]. Human pluripotent stem cells, including iPSCs and ESCs, could offer unlimited sources for this purpose [102].…”

“…Therefore, there are requirements for the generation of CAR cells from other sources, which enables the expansion of this immunotherapy to a larger number of patients [9,102]. Human pluripotent stem cells, including iPSCs and ESCs, could offer unlimited sources for this purpose [102].…”

Stem Cell Therapy

“…The engineered cells are then reinfused into the patient and supposed to eliminate the cancerous cells. As the whole procedure of engineering is very timeconsuming, several groups are working on protocols for differentiating iPSCs into T cells which can then be modified to express the chimeric receptor (Iriguchi and Kaneko 2019). A clinical trial with these cells has been already announced by a Japanese cooperation between the Center for iPS Cell Research and Application (CiRA) and Takeda (Kobayashi et al 2019).…”

Peptide Presentation to T Cells: Solving the Immunogenic Puzzle

“…That is to say, for many years we have relied upon empirical study of peptides to determine their immunogenicity, have unraveled the steps in antigen processing and peptide loading in great detail, have understood at a structural level MHC–peptide interactions and generalizations versus discrepancies in the docking of TCRs onto this complex, as well as the signaling cascade and cell fate that ensues . In characterizing thousands of T cell responses, immunologists have gained insight into phenomena such as immunodominance (the disproportionate skewing of responses in individuals and populations of individuals toward specific epitopes) and have begun to tread the tantalizing ground of harnessing T cells for tumor immunotherapy . Yet, at a fundamental level, where has this left our understanding?…”

“…[15][16][17][18] In characterizing thousands of T cell responses, immunologists have gained insight into phenomena such as immunodominance (the disproportionate skewing of responses in individuals and populations of individuals toward specific epitopes) [19] and have begun to tread the tantalizing ground of harnessing T cells for tumor immunotherapy. [20,21] Yet, at a fundamental level, where has this left our understanding? Such monumental achievements, if anything, serve to highlight a number of key questions in antigen presentation and T cell immunity that remain unsolved.…”