# A phase I clinical trial to evaluate the tolerability and safety of an allogeneic iPSC-derived iNKT cell and α-GalCer-pulsed autologous DC combination therapy for patients with recurrent and advanced head and neck cancer: A study protocol

**Authors:** Tomoya Kurokawa, Tomohisa Iinuma, Haruna Ebisu, Tomoha Yanagidaira, Yosuke Inaba, Tadami Fujiwara, Yoko Hattori, Tominaga Fukazawa, Takahiro Aoki, Haruhiko Koseki, Hideki Hanaoka, Toyoyuki Hanazawa, Shinichiro Motohashi, Maria de Fátima Macedo, Maria de Fátima Macedo, Maria de Fátima Macedo, Maria de Fátima Macedo

PMC · DOI: 10.1371/journal.pone.0342387 · PLOS One · 2026-02-26

## TL;DR

This clinical trial tests the safety of a new cancer treatment combining lab-made NKT cells and dendritic cells in patients with advanced head and neck cancer.

## Contribution

The study introduces a novel iPSC-derived iNKT cell and α-GalCer-pulsed DC combination therapy for cancer treatment in humans.

## Key findings

- The trial aims to assess the tolerability and safety of iPSC-iNKT cells combined with α-GalCer-pulsed DCs in cancer patients.
- The treatment involves nasal submucosal DC/Gal injection followed by intra-arterial iPSC-iNKT cell administration.
- The study will provide foundational data for future clinical applications of iPSC-derived iNKT cells in cancer therapy.

## Abstract

Natural killer T (NKT) cells show intense tumor-killing activity through direct and indirect pathways. However, humans have less than 0.01% of NKT cells in the peripheral blood, making it difficult to apply NKT cells for cancer treatment. We have successfully produced invariant NKT cells derived from induced pluripotent stem cells (iPSC-iNKT cells) and demonstrated the tolerability of this product in a previous phase 1 clinical trial. Although the iPSC-iNKT cells showed substantial anti-tumor activity against various tumor cell types when combined with α-Galactosylceramide-pulsed autologous dendritic cells (DC/Gal) in non-clinical experiments, the tolerability of this combination therapy for humans has not demonstrated yet. Thus, we planned this first-in-human phase 1 open-label clinical trial to demonstrate data on tolerability and safety, as well as explore the immunological changes that occur following this combination treatment. We hypothesize that the sequential induction of nasal submucosal DC/Gal injection and intra-arterial administration of the iPSC-iNKT cells is tolerable and has a favorable safety profile for cancer patients. This trial provides vital and fundamental information for next-phase clinical trials and future applications of iPSC-iNKT cells for various cancer patients (jRCTa030220741; URL: https://jrct.mhlw.go.jp/en-latest-detail/jRCTa030220741).

## Linked entities

- **Chemicals:** α-Galactosylceramide (PubChem CID 2826713)
- **Diseases:** head and neck cancer (MONDO:0005627)

## Full-text entities

- **Genes:** IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, HLA-A (major histocompatibility complex, class I, A) [NCBI Gene 3105] {aka HLAA}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, GAL (galanin and GMAP prepropeptide) [NCBI Gene 51083] {aka ETL8, GAL-GMAP, GALN, GLNN, GMAP}, SLC17A5 (solute carrier family 17 member 5) [NCBI Gene 26503] {aka AST, ISSD, NSD, SD, SIALIN, SIASD}, CD1D (CD1d molecule) [NCBI Gene 912] {aka R3, R3G1}, HLA-B (major histocompatibility complex, class I, B) [NCBI Gene 3106] {aka AS, B-4901, HLAB}, TRBV20OR9-2 (T cell receptor beta variable 20/OR9-2 (non-functional)) [NCBI Gene 6962] {aka CDR3, TCRBV20S2, TCRBV2O, TCRBV2S2O}, GPT (glutamic--pyruvic transaminase) [NCBI Gene 2875] {aka AAT1, ALT, ALT1, GPT1, SGPT}, HLA-C (major histocompatibility complex, class I, C) [NCBI Gene 3107] {aka D6S204, HLA-JY3, HLAC, HLC-C, MHC, PSORS1}
- **Diseases:** tumor lysis syndrome (MESH:D015275), DLT (MESH:D045745), unstable angina (MESH:D000789), kidney disfunction (MESH:D007674), interstitial lung disease (MESH:D017563), allergy (MESH:D004342), cardiac disease (MESH:D006331), AEs (MESH:D064420), Wolff-Parkinson-White (WPW) syndrome (MESH:D014927), laboratory abnormalities (MESH:D007757), blood toxicity (MESH:D006402), death (MESH:D003643), squamous cell carcinomas (MESH:D002294), head and neck squamous cell carcinoma (MESH:D000077195), non-small cell lung cancer (MESH:D002289), CRS (MESH:D003398), vomiting (MESH:D014839), autoimmune disease (MESH:D001327), nausea (MESH:D009325), IDMC (MESH:D064129), A-V block (MESH:D006327), diarrhea (MESH:D003967), Breathlessness (MESH:D004417), poorly controlled diabetes mellitus (MESH:D003920), left bundle branch block (MESH:D002037), lung disease (MESH:D008171), Tumor (MESH:D009369), Head and Neck Cancer (MESH:D006258)
- **Chemicals:** nivolumab (MESH:D000077594), steroid (MESH:D013256), DC (MESH:D003841), lipid (MESH:D008055), pembrolizumab (MESH:C582435), cetuximab (MESH:D000068818), creatine (MESH:D003401), PONE-D-25-33703R2 (-), glycolipid (MESH:D006017), methylprednisolone (MESH:D008775), Gal (MESH:C101993), bilirubin (MESH:D001663), alpha-GalCer (MESH:C493154), PS (MESH:D010758)
- **Species:** Homo sapiens (human, species) [taxon 9606], Human immunodeficiency virus (species) [taxon 12721], Hepatitis B virus (no rank) [taxon 10407], Human immunodeficiency virus 1 (no rank) [taxon 11676], Mycoplasma (genus) [taxon 2093], Mus musculus (house mouse, species) [taxon 10090], Human T-cell leukemia virus type I (no rank) [taxon 11908], Hepatitis C Virus [taxon 11103]
- **Cell lines:** Shi-scid — Homo sapiens (Human), Adult acute monocytic leukemia, Cancer cell line (CVCL_2191)

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12944769/full.md

## References

22 references — full list in the complete paper: https://tomesphere.com/paper/PMC12944769/full.md

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Source: https://tomesphere.com/paper/PMC12944769