Currently, we focus on developing NKT cell-targeted immunotherapy for cancer to improve clinical outcomes. Our previous clinical trials using patient-derived peripheral blood NKT cells showed difficulty in preparing a sufficient quantity of functionally capable NKT cells from patients with advanced cancer. In 2016, a robust protocol was successfully established to generate NKT cells in vitro using iPS cells. This achievement allowed us to ensure sufficient expansion of NKT cells. These iPS cell-derived NKT cells (iPS-NKT cells) can be activated by ligand-pulsed DCs, resulting in significant IFN-γ production upon activation, and exhibit enhanced cytotoxic activity against various tumors both in vitro and in vivo.
Based on these preclinical examinations, a Phase I study of iPS-NKT cells was initiated in 2020 for patients with advanced or recurrent HNC refractory to standard treatment. The trial is now enrolling patients to assess the feasibility and safety of intra-arterial injection of iPS-NKT cells, with completion anticipated by the end of this fiscal year.
To elicit the adjuvant activity of NKT cells more efficiently, a preclinical model combining iPS-NKT cells with αGalCer-pulsed DCs was established. In this model, human iPS-NKT cells stimulated with αGalCer-pulsed DCs showed a potent indirect anti-tumor effect, inducing tumor-reactive memory phenotype T cells. These promising results paved the way for the clinical trial of the combination therapy with iPS-NKT cells plus autologous αGalCer-pulsed antigen-presenting cells.
In this talk, the strategies employed and future perspectives for NKT cell-targeting immunotherapy will be discussed.