Interleukin-7 expression by CAR-T cells improves CAR-T cell survival and efficacy in chordoma.
B7–H3
Chimeric antigen receptor T cells
Chordoma
Interleukin-7
Journal
Cancer immunology, immunotherapy : CII
ISSN: 1432-0851
Titre abrégé: Cancer Immunol Immunother
Pays: Germany
ID NLM: 8605732
Informations de publication
Date de publication:
02 Aug 2024
02 Aug 2024
Historique:
received:
24
04
2024
accepted:
06
06
2024
medline:
2
8
2024
pubmed:
2
8
2024
entrez:
2
8
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 39093440
doi: 10.1007/s00262-024-03756-9
pii: 10.1007/s00262-024-03756-9
doi:
Substances chimiques
Interleukin-7
0
Receptors, Chimeric Antigen
0
IL7 protein, human
0
B7 Antigens
0
CD276 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
188Subventions
Organisme : Beijing Natural Science Foundation-Haidian Original Innovation Joint Fund
ID : No.L232141
Organisme : Beijing Natural Science Foundation-Haidian Original Innovation Joint Fund
ID : No: L212039
Organisme : Beijing Hospitals Authority Clinical medicine Development of special funding support
ID : XMLX202138
Informations de copyright
© 2024. The Author(s).
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