Using Human Induced Pluripotent Stem Cells for the Generation of Tumor Antigen-specific T Cells

Abstract

The generation and expansion of functional T cells in vitro can lead to a broad range of clinical applications. One such use is for the treatment of patients with advanced cancer. Adoptive T cell transfer (ACT) of highly enriched tumor antigen-specific T cells has been shown to cause durable regression of metastatic cancer in some patients. However, during expansion, these cells may become exhausted or senescent, limiting their effector function and persistence in vivo. Induced pluripotent stem cell (iPSC) technology may overcome these obstacles by leading to in vitro generation of large numbers of less differentiated tumor antigen-specific T cells. Human iPSC (hiPSC) have the capacity to differentiate into any type of somatic cell, including lymphocytes, which retain the original T cell receptor (TCR) genomic rearrangement when a T cell is used as a starting cell. Therefore, reprogramming of human tumor antigen-specific T cells to hiPSC followed by redifferentiation to T cell lineage has the potential to produce rejuvenated tumor antigen-specific T cells. Described here is a method for generating tumor antigen-specific CD8αβ + single positive (SP) T cells from hiPSC using OP9/DLL1 co-culture system. This method is a powerful tool for in vitro T cell lineage generation and will facilitate the development of in vitro derived T cells for use in regenerative medicine and cell-based therapies.

Self-organized yolk sac-like organoids allow for scalable generation of multipotent hematopoietic progenitor cells from human induced pluripotent stem cells

“…Additionally, at the time of this study there was no published work indicating whether hBM-MSCs can induce hematopoiesis of hiPSC similar to OP9 cells. Based on our experience of using the classical OP9 co-culture system (Good et al, 2019), we reasoned that the gradual loss of stem cell properties in hBM-MSCs during expansion may be detrimental. Therefore, we limited the expansion of hBM-MSCs to 4-5 passages prior to Hp-spheroid formation (Sabatino et al, 2012).…”

Immune Cell Generation from Human-Induced Pluripotent Stem Cells: Current Status and Challenges

“…The results demonstrated that iPSCs are a potent tool for generating and developing T-cell lineages in vitro. This advancement holds great potential in the field of regenerative medicine, particularly for the progress of allogeneic therapies [37].…”

Single-Cell TCR and Transcriptome Analysis: An Indispensable Tool for Studying T-Cell Biology and Cancer Immunotherapy

“…Typically, only one third of the wells contain a single cell when starting with a concentration of 0.5 cells per aliquot ( 18 ). Micromanipulation is another technique developed mainly to isolate embryos or stem cells, but it could be applied to T cells, particularly since the potential of generating human induced pluripotent stem cells to differentiate into anti-tumor T cells has been explore ( 19 ). A microscope-guided capillary pipette is used to pick single cells from a suspension culture ( 20 ).…”