Poster Presentation CD1-MR1 Workshop 2025

Single-cell analysis results of the patient's blood in the phase I clinical trial of allogeneic iPS cell-derived invariant NKT cell monotherapy (#151)

Takahiro Aoki 1 2 , Tomohisa Iinuma 1 , Haruhiko Koseki 2 , Shinichiro Motohashi 1
  1. Chiba University, Chiba, CHIBA, Japan
  2. Laboratory for Developmental Genetics, RIKEN, Yokohama, Kanagawa, Japan

Invariant NKT cells demonstrate antitumor activity through their intrinsic cytotoxicity and adjuvant properties. To evaluate the safety and tolerability of clinical-grade iNKT cells generated from induced pluripotent stem cells (iPSC-iNKT cells), we conducted the phase I clinical trial of allogeneic iPSC-iNKT cells in patients with recurrent head and neck cancer. In three out of ten enrolled patients for whom samples were available before administration and 8 and 21 days after administration, peripheral blood T cells and NK cells were submitted for single-cell RNA sequencing and TCR sequencing. In all three patients' NK cells and T cells, the IFN-γ pathway was activated after iPSC-iNKT cell administration. In the two patients, clonal expansion of CD8 T cells was identified. Although this trial's antitumor effect was weak because of iNKT cell monotherapy, we found that iPSC-iNKT cells can induce T-cell clonal expansion. In the future, we intend to enhance this adjuvant effect by combining therapy with αGalCer-pulsed antigen-presenting cells.