Induced Pluripotent Stem Cell-derived CAR-Macrophage Cells with Antigen-dependent Anti-Cancer Cell Functions for Liquid and Solid Tumors

Abstract

One sentence summary:We developed CAR-expressing iPSC-induced macrophage cells that have antigen-dependent phagocytosis and pro-inflammatory functions and anti-cancer cell activity for both liquid and solid tumor cells. Abstract:The Chimera antigen receptor (CAR)-T cell therapy has gained great success in the clinic. However, there are still major challenges for its wider applications in a variety of cancer 2 types including lack of effectiveness due to the highly complex tumor microenvironment, and the forbiddingly high cost due to personalized manufacturing procedures. In order to overcome these hurdles, numerous efforts have been spent focusing on optimizing Chimera Antigen Receptors, engineering and improving T cell capacity, exploiting features of subsets of T cell or NK cells, or making off-the-shelf universal T cells. Here, we developed induced pluripotent stem cells (iPSCs)-derived, CAR-expressing macrophage cells (CAR-iMac). These cells showed antigen-dependent macrophage functions such as expression and secretion of cytokines, polarization toward the pro-inflammatory/anti-tumor state, and phagocytosis of tumor cells, as well as some in vivo anti-cancer cell activity for both liquid and solid tumors. This technology platform for the first time provides an unlimited source of iPSC-derived engineered CARmacrophage cells which could be utilized to eliminate cancer cells or modulate the tumor microenvironment in liquid and solid tumor immunotherapy.

Challenges and Opportunities for Immunotherapeutic Intervention against Myeloid Immunosuppression in Glioblastoma

“…For these reasons, other cell types are being evaluated as platforms for CARs in other diseases. Interestingly, CAR-Macs have been described [55,56]. CAR-enhanced phagocytosis is a way to kill tumor cells, although there is a limit to the number of large tumor cells that can be ingested by each individual Mac, whereas T cells 'serially kill' through repeated target cell contacts [53,54].…”

A Bird’s-Eye View of Cell Sources for Cell-Based Therapies in Blood Cancers

“…In the same year, Themeli et al [111] successfully combined iPSCs and CAR technologies to produce human T cells that target CD19 in malignant B cells. A recent publication by Li Zhang et al [157] obtained functional macrophages of iPSC derived from peripheral blood mononuclear cells. These macrophages were engineered for the expression of CD19 CAR to trigger phagocytosis after tumor antigen recognition in leukemia cell lines Nalm6 and K562.…”