Recently, therapeutic strategy for melanoma is markedly advanced, and unresectable and distant metastatic melanomas can be treated using BRAF and MEK inhibitors, and immune checkpoint modulators, such as anti-PD-1 and anti-CTLA-4 antibodies. In addition, adoptive immunotherapy using tumor antigen-specific cytotoxic T cells is also developing. However, treatment efficacy of anti-cancer agents and adoptive immunotherapies are still limited. Moreover, there are several issues for commercial viability of adoptive immunotherapy, especially in the case using T cell receptor gene-modified T cells. 
Induced pluripotent stem cells (iPSCs) are artificial stem cells generated from somatic cells by exogenous expression of reprogramming factors, and have a great potential to differentiate all types of cell needed for research field and regenerative therapy. Recently, it has been reported that iPSCs can be generated from established CD8+ T cell lines recognizing MART-1, one of cancer-testis antigens expressed in melanoma, and re-differentiated into rejuvenated T cells to provide enough number of functional T cells for adoptive immunotherapy. However, it is unclear whether tumor antigen-specific T cells can be enough in number and freshly isolated from MHC-unidentified patients with melanoma, and reprogrammed into iPSCs. 
In this study, we succeeded in isolating NY-ESO-1-specific CD8+ T cells from a Japanese melanoma patient having minor HLA types without the usage of MHC-dependent tetramer technology widely used for antigen-specific T cell isolation. We next generated transgene-free iPSCs from isolated T cells using Sendai virus vectors, and checked the authenticity of generated iPSCs by the expression of stem cell markers and the differentiation capability into all three germ layers. Moreover, we confirmed that T cell receptor gene sequence in T cell-derived iPSCs maintains compared to that in isolated T cells, even after reprogramming process. We are now in the process for re-differentiating T cell-derived iPSCs into functional cytotoxic T cells using the co-culture system with OP9 cell lines. 
Our study is capable of being a “touchstone” to develop iPSC-based adoptive immunotherapy for the treatment of melanoma for the future clinical use.

Generation of induced pluripotent stem cells (iPSCs) from NY-ESO-1-specific CD8+ T cell isolated from the patient with melanoma