机构:[1]Capital Med Univ, Xuanwu Hosp, Dept Neurosurg, Beijing, Peoples R China首都医科大学宣武医院[2]China Int Neurosci Inst CHINA INI, Lab Spinal Cord Injury & Funct Reconstruct, Beijing, Peoples R China[3]Capital Med Univ, Xuanwu Hosp, Dept Otorhinolaryngol Head & Neck Surg, Beijing, Peoples R China首都医科大学宣武医院
Chordoma is a rare bone tumor that frequently recurs after surgery, and the prognosis is poor with current treatments. This study aimed to identify potential novel immunotherapeutic targets for chordomas by identifying target proteins in clinical samples as well as tumor microenvironmental factors to enhance efficacy. Fourteen chordoma samples were analyzed by single-cell RNA sequencing, and B7-H3 and IL-7 were identified as potential targets and potentiators, respectively. B7-H3-targeted chimeric antigen receptor T (CAR-T) cells and B7-H3 CAR-T cells expressing IL-7 were synthesized and their anti-tumor activity evaluated in vitro, including in primary chordoma organoid models. The B7-H3 CAR-T/IL-7 therapy showed enhanced cytotoxicity and prolonged duration of action against tumor cells. Additionally, IL-7 modulated favorable subpopulations of cultured CAR-T cells, diminished immune checkpoint expression on T-cell surfaces, and enhanced T-cell functionality. The incorporation of IL-7 molecules into the B7-H3 CAR structure augmented CAR-T-cell function and improved CAR-T-cell efficacy, thus providing a novel dual therapeutic strategy for chordoma treatment.
基金:
Beijing Natural Science Foundation-Haidian Original Innovation Joint Fund [L212039, L232141]; Beijing Hospitals Authority Clinical medicine Development of special funding support [XMLX202138]
第一作者机构:[1]Capital Med Univ, Xuanwu Hosp, Dept Neurosurg, Beijing, Peoples R China[2]China Int Neurosci Inst CHINA INI, Lab Spinal Cord Injury & Funct Reconstruct, Beijing, Peoples R China
通讯作者:
通讯机构:[1]Capital Med Univ, Xuanwu Hosp, Dept Neurosurg, Beijing, Peoples R China[2]China Int Neurosci Inst CHINA INI, Lab Spinal Cord Injury & Funct Reconstruct, Beijing, Peoples R China
推荐引用方式(GB/T 7714):
Wu Huantong,Xu Zhuofan,Qi Maoyang,et al.Interleukin-7 expression by CAR-T cells improves CAR-T cell survival and efficacy in chordoma[J].CANCER IMMUNOLOGY IMMUNOTHERAPY.2024,73(10):doi:10.1007/s00262-024-03756-9.
APA:
Wu, Huantong,Xu, Zhuofan,Qi, Maoyang,Liu, Penghao,Zhang, Boyan...&Chen, Zan.(2024).Interleukin-7 expression by CAR-T cells improves CAR-T cell survival and efficacy in chordoma.CANCER IMMUNOLOGY IMMUNOTHERAPY,73,(10)
MLA:
Wu, Huantong,et al."Interleukin-7 expression by CAR-T cells improves CAR-T cell survival and efficacy in chordoma".CANCER IMMUNOLOGY IMMUNOTHERAPY 73..10(2024)