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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.
Objective:
chordomas are rare bone tumors with few therapeutic options. Skull base and sacrum are the two most common origin sites. Immunotherapies are emerging as the most promising approaches to fight various cancers. This study tends to identify new cell surface targets for immunotherapeutic options of skull base chordomas.
Methods:
we profiled 45 skull base chordoma clinical samples by immunohistochemistry for the expression of six CAR-Targets (PD-L1, B7-H3, B7-H4, VISTA, HER2 and HER3). In addition, we generated B7-H3 targeted CAR-T-cells and evaluated their antitumor activities in vitro.
Results:
We found that B7-H3 was positively stained in 7 out of 45 (16%) chordoma samples and established an expression hierarchy for these antigens (B7-H3 > HER3 > PD-L1 > HER2 = VISTA = B7-H4). We then generated a B7-H3 targeted CAR vector and demonstrated that B7-H3-CAR-T-cells recognized antigen positive cells and exhibited significant antitumor effects, including suppression of tumor spheroid formation, CAR-T-cell activation and cytokine secretion.
Conclusions:
Our results support B7-H3 might serve as a promising target for CAR-T-cell therapies against chordomas.
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.
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