Invariant NKT cell-based effector T cell expressing a tumor reactive T cell receptor, as a possible cell medicine for pancreatic cancer

目前，癌症抗原衍生的T细胞表位肽疫苗正在开发中，并且已经进行了临床试验。不幸的是，结果令人失望。为了解决这些问题，我们专注于识别由CD 1d呈递的α-GalCer的不变NKT细胞。我们建立了基于iNKT细胞的抗肿瘤效应T细胞，其表达肿瘤反应性T细胞受体（TCR）。TCR转导的CD 4-CD 8-（DN）iNKT细胞对于肿瘤抗原特异性细胞毒性是优异的。相比之下，TCR转导的CD 4 + CD 8-（CD 4）iNKT细胞充当细胞佐剂，在α-GalCer负载的树突细胞中诱导稳健的IL-12 p70产生。表达肿瘤反应性TCR的iNKT细胞发挥细胞毒活性和佐剂活性，可能是癌症免疫治疗的有力工具。

Currently, cancer antigen-derived T cell epitope peptide vaccines are under development and clinical trials have already been performed. Unfortunately, outcomes have been disappointing. To address these issues, we focused on invariant NKT cells that recognize alpha-GalCer presented by CD1d. We established iNKT cell-based anti-tumor effector T cells that express a tumor reactive T cell receptor (TCR). The TCR-transduced CD4-CD8- (DN) iNKT cells were excellent for tumor antigen-specific cytotoxicity. In contrast, the TCR-transduced CD4+CD8- (CD4) iNKT cells acted as a cellular adjuvant inducing robust IL-12p70 production in alpha-GalCer-loaded dendritic cells. Tumor-reactive TCR-expressing iNKT cell that exert cytotoxic activity and adjuvant activity may be a powerful tool for cancer immunotherapy.