4.6 Review

Engineering Induced Pluripotent Stem Cells for Cancer Immunotherapy

Journal

CANCERS
Volume 14, Issue 9, Pages -

Publisher

MDPI
DOI: 10.3390/cancers14092266

Keywords

induced pluripotent stem cell (iPSC); immunotherapy; cancer; allogeneic; off-the-shelf; reprogramming; chimeric antigen receptor (CAR); T; natural killer (NK); invariant natural killer T (iNKT); gamma delta T (gamma delta T); mucosal-associated invariant T (MAIT); macrophages (M phi s)

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Funding

  1. University of California, Los Angeles (UCLA)

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Cell-based immunotherapy has revolutionized the treatment of hematological malignancies, but obstacles remain in the widespread clinical applications of current autologous therapies. Human induced pluripotent stem cells offer a potential solution by providing a scalable source for cell therapy, and recent advances have been made in using these cells for immune therapy, particularly in combination with CAR-engineering.
Cell-based immunotherapy, such as chimeric antigen receptor (CAR) T cell therapy, has revolutionized the treatment of hematological malignancies, especially in patients who are refractory to other therapies. However, there are critical obstacles that hinder the widespread clinical applications of current autologous therapies, such as high cost, challenging large-scale manufacturing, and inaccessibility to the therapy for lymphopenia patients. Therefore, it is in great demand to generate the universal off-the-shelf cell products with significant scalability. Human induced pluripotent stem cells (iPSCs) provide an unlimited supply for cell therapy because of their unique self-renewal properties and the capacity to be genetically engineered. iPSCs can be differentiated into different immune cells, such as T cells, natural killer (NK) cells, invariant natural killer T (iNKT) cells, gamma delta T (gamma delta T), mucosal-associated invariant T (MAIT) cells, and macrophages (M phi s). In this review, we describe iPSC-based allogeneic cell therapy, the different culture methods of generating iPSC-derived immune cells (e.g., iPSC-T, iPSC-NK, iPSC-iNKT, iPSC-gamma delta T, iPSC-MAIT and iPSC-M phi), as well as the recent advances in iPSC-T and iPSC-NK cell therapies, particularly in combinations with CAR-engineering. We also discuss the current challenges and the future perspectives in this field towards the foreseeable applications of iPSC-based immune therapy.

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