B7-H3 as a Target for CAR-T Cell Therapy in Skull Base Chordoma

Cheng Long1, Gaowei Li2, Chengyun Zhang1

  • 1Orthopedics Department, West China Hospital, Sichuan University, Chengdu, China.

Frontiers in Oncology
|December 6, 2021
PubMed
Abstract

Insights

Researchers identified B7-H3 as a promising target for chordoma immunotherapy. B7-H3 targeted CAR-T-cells showed significant antitumor effects in preclinical models, offering new hope for treating these rare bone tumors.

Area of Science:

  • Oncology
  • Immunotherapy
  • Cancer Biology

Background:

  • Chordomas are rare bone tumors with limited treatment options.
  • Immunotherapy presents a promising avenue for cancer treatment.
  • Skull base and sacrum are common sites for chordoma development.

Purpose of the Study:

  • To identify novel cell surface targets for immunotherapy in skull base chordomas.
  • To evaluate the potential of B7-H3 as a target for chimeric antigen receptor (CAR)-T-cell therapy.

Main Methods:

  • Immunohistochemistry profiling of 45 skull base chordoma samples for six CAR targets.
  • Generation and in vitro evaluation of B7-H3 targeted CAR-T-cells.

Main Results:

  • B7-H3 expression was detected in 16% of chordoma samples.
  • An expression hierarchy of antigens was established: B7-H3 > HER3 > PD-L1 > HER2 = VISTA = B7-H4.
  • B7-H3-CAR-T-cells demonstrated antigen recognition and significant antitumor activity, including suppressed tumor spheroid formation and cytokine secretion.

Conclusions:

  • B7-H3 is a potential therapeutic target for chordoma.
  • CAR-T-cell therapy targeting B7-H3 shows promise for treating chordomas.