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Interleukin-7 expression by CAR-T cells improves CAR-T cell survival and efficacy in chordoma

Huantong Wu1,2, Zhuofan Xu1,2, Maoyang Qi1,2

  • 1Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China.

Cancer Immunology, Immunotherapy : CII
|August 2, 2024
PubMed

Insights

This study identifies B7-H3 as a target and IL-7 as a potentiator for chordoma immunotherapy. Combining B7-H3-targeted chimeric antigen receptor T (CAR-T) cells with IL-7 shows enhanced anti-tumor activity.

Area of Science:

  • Oncology
  • Immunology
  • Biotechnology

Background:

  • Chordoma is a rare bone tumor with poor prognosis and high recurrence rates after surgery.
  • Current treatments for chordoma are limited, necessitating novel therapeutic strategies.

Purpose of the Study:

  • To identify novel immunotherapeutic targets for chordoma.
  • To explore the potential of B7-H3 as a target and IL-7 as a potentiator for enhancing chordoma treatment efficacy.

Main Methods:

  • Single-cell RNA sequencing was performed on fourteen chordoma samples.
  • B7-H3-targeted chimeric antigen receptor T (CAR-T) cells and B7-H3 CAR-T cells expressing IL-7 were synthesized.
  • In vitro anti-tumor activity was evaluated using primary chordoma organoid models.

Main Results:

  • B7-H3 and IL-7 were identified as potential targets and potentiators, respectively.
  • B7-H3 CAR-T/IL-7 therapy demonstrated enhanced cytotoxicity and prolonged action against chordoma cells.
  • IL-7 improved CAR-T cell function, reduced immune checkpoint expression, and enhanced T-cell activity.

Conclusions:

  • A novel dual therapeutic strategy combining B7-H3 CAR-T cells with IL-7 offers improved efficacy for chordoma treatment.
  • This approach enhances CAR-T cell function and provides a promising avenue for managing chordoma.
Keywords:
B7–H3Chimeric antigen receptor T cellsChordomaInterleukin-7

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