Cancer therapy using regenerated immune cells from induced pluripotent stem cells

Induced pluripotent stem cells (iPSCs) can unlimitedly self-renew and differentiate into various cell types. One of the possible applications of iPSCs is its potential use in generating various types of immune cells for cancer therapy. iPSC-derived immune cells can be used for gene manipulation to enhance their efficacy and safety, and can stably provide the desired amount of cell preparation of validated quality.

We recently established a method to generate invariant natural killer T (iNKT) cells from iPSCs (1). The re-differentiated iNKT cells (re-iNKT cells) expressed an invariant T cell receptor (TCR) and recognized a specific glycolipid presented by a monomorphic CD1d. Therefore, re-iNKT cells genetically engineered to express a tumor antigen-specific TCR or a chimeric antigen receptor, are potentially utilized for cancer immunotherapy without deleterious graft versus host diseases.

We also established a method to generate myeloid cells with proliferation capacity from iPSCs (2). Genetically engineered iPSC-derived proliferating myeloid cells with immune-modulatory functions may actively influence on host immune system leading therapeutic effects.

1. Kitayama S, Zhang R, Liu TY, Ueda N, Iriguchi S, Yasui Y, Kawai Y, Tatsumi M, Hirai N, Mizoro Y, Iwama T, Watanabe A, Nakanishi M, Kuzushima K, Uemura Y, Kaneko S. Cellular Adjuvant Properties, Direct Cytotoxicity of Re-differentiated Vα24 Invariant NKT-like Cells from Human Induced Pluripotent Stem Cells. Stem Cell Reports 6: 213-27, 2016 https://www.ncbi.nlm.nih.gov/pubmed/26862702

2. Zhang R, Liu TY, Senju S, Haruta M, Hirosawa N, Suzuki M, Tatsumi M, Ueda N, Maki H, Nakatsuka R, Matsuoka Y, Sasaki Y, Tsuzuki S, Nakanishi H, Araki R, Abe M, Akatsuka Y, Sakamoto Y, Sonoda Y, Nishimura Y, Kuzushima K, Uemura Y. Generation of mouse pluripotent stem cell-derived proliferating myeloid cells as an unlimited source of functional antigen-presenting cells. Cancer Immunol Res. 6: 668-77, 2015 https://www.ncbi.nlm.nih.gov/pubmed/25672396