Reference - Detail
| RRC ID | 83315 |
|---|---|
| Author | Kuroda H, Kijima N, Tachi T, Ikeda S, Murakami K, Nakagawa T, Yaga M, Nakagawa K, Utsugi R, Hirayama R, Okita Y, Kagawa N, Hosen N, Kishima H. |
| Title | Prostaglandin F2 receptor negative regulator as a potential target for chimeric antigen receptor-T cell therapy for glioblastoma. |
| Journal | Cancer Immunol Immunother |
| Abstract |
BACKGROUND:Chimeric antigen receptor (CAR)-T cell therapy targeting novel glioblastoma (GBM)-specific cell surface antigens is a promising approach. However, transcriptome analyses have revealed few GBM-specific target antigens. METHODS:A library of monoclonal antibodies (mAbs) against tumor cell lines derived from patients with GBM was generated. mAbs reacting with tumor cells in resected tissues from patients with GBM but not with nonmalignant human brain cells were detected. The antigens that were recognized were identified through expression cloning. CAR-T cells derived from a candidate mAb were generated, and their functionality was tested in vitro and in vivo. RESULTS:Approximately 3,200 clones were established. Among them, 5E17 reacted with tumor cells in six of seven patients with GBM, but not with nonmalignant human brain cells. Prostaglandin F2 receptor negative regulator (PTGFRN) was identified as an antigen recognized by 5E17. CAR-T cells derived from 5E17 produced cytokines and exerted cytotoxicity upon co-culture with tumor cells from patients with GBM. Furthermore, intracranial injection of 5E17-CAR-T cells demonstrated antitumor effects in an orthotopic xenograft murine model with patient-derived GBM cells. CONCLUSIONS:Cell surface PTGFRN is a candidate target for intracranial CAR-T cell therapy for GBM. On-target off-tumor toxicity in alternative normal tissues needs to be carefully tested. |
| Volume | 74(4) |
| Pages | 136 |
| Published | 2025-3-6 |
| DOI | 10.1007/s00262-025-03979-4 |
| PII | 10.1007/s00262-025-03979-4 |
| PMID | 40047938 |
| PMC | PMC11885767 |
| MeSH | Animals Antibodies, Monoclonal / immunology Brain Neoplasms* / immunology Brain Neoplasms* / pathology Brain Neoplasms* / therapy Cell Line, Tumor Female Glioblastoma* / immunology Glioblastoma* / pathology Glioblastoma* / therapy Humans Immunotherapy, Adoptive* / methods Male Mice Receptors, Chimeric Antigen* / immunology Receptors, Chimeric Antigen* / metabolism T-Lymphocytes* / immunology Xenograft Model Antitumor Assays |
| IF | 5.442 |
| Resource | |
| Human and Animal Cells | Ba/F3 |