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Bispecific ANXA2/CD147 CAR-T cell therapy for osteosarcoma
Hai-Jun Tang1, Wei Dai1, Dan-Ting Xiao1
1Department of Spine and Osteopathic Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Oncogene
|August 3, 2026
Summary
A new bispecific CAR-T cell therapy targeting ANXA2 and CD147 shows enhanced efficacy against osteosarcoma. This novel approach offers improved antitumor activity and a promising strategy for osteosarcoma immunotherapy.
Area of Science:
- Oncology
- Immunotherapy
- Cellular Therapy
Background:
- Osteosarcoma is a highly malignant bone cancer with a poor prognosis.
- Current single-target CAR-T cell therapies for osteosarcoma have limited efficacy.
Purpose of the Study:
- To develop and evaluate a novel bispecific CAR-T cell therapy targeting ANXA2 and CD147 for osteosarcoma.
- To provide an experimental basis for improving osteosarcoma treatment outcomes.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) identified ANXA2 and CD147 as osteosarcoma antigens.
- A bispecific ANXA2/CD147 CAR-T construct was generated and validated.
- In vitro cytotoxicity assays and in vivo xenograft models (CDX, PDX) were used to assess efficacy.
Main Results:
- Bispecific CAR-T cells demonstrated significantly greater cytotoxicity and released higher levels of effector molecules (GZMB, TNFα) compared to single-target controls.
- In vivo studies showed superior antitumor activity, reduced tumor growth, and decreased metastasis.
- Increased infiltration of M1 macrophages was observed in tumors treated with bispecific CAR-T cells.
Conclusions:
- A bispecific ANXA2/CD147 CAR-T cell was successfully generated with potent antitumor activity.
- This novel CAR-T cell therapy presents a promising new strategy for osteosarcoma immunotherapy.
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