Folate Receptor-Alpha Targeted 7x19 CAR-γδT Suppressed Triple-Negative Breast Cancer Xenograft Model in Mice
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Dynamic Imaging of Chimeric Antigen Receptor T Cells with [18F]Tetrafluoroborate Positron Emission Tomography/Computed Tomography
Published on: February 17, 2022
Xueshuai Ye1,2, Xinna Deng2, Junye Wen2
1Department of Surgery, Hebei Medical University, Shijiazhuang 050051, Hebei Province, China.
Background:
Triple-negative breast cancer (TNBC) is the worst prognosis subtype of breast cancer due to lack of specific targets. Recent studies have shown that immunotherapy may solve that problem by targeting folate receptor-alpha (FRα).
Methods:
Gene modified γδ T cells were manufactured to express FRa specific chimeric antigen receptor (FRa CAR) and secrete interleukin-7 (IL-7) and chemokine C-C motif ligand 19 (CCL19). CAR-γδT cells that secrete IL-7 and CCL19 (7 × 19 CAR-γδT) were evaluated for their antitumor activity both in vitro and in vivo.
Results:
7 × 19 CAR-γδT showed remarkable antitumor activity in vitro. Combined with PBMC, 7 × 19 CAR-γδT inhibited TNBC xenograft model growth superiorly compared with single-application or conventional CAR-γδT cells. Histopathological analyses showed increased DC or T cells infiltration to tumor tissues.
Conclusion:
Taken together, our results showed that 7 × 19 CAR-γδT have remarkable anti-TNBC tumor activity and showed a broad application prospect in the treatment of incurable TNBC patients.
Insights
Engineered gamma-delta T cells targeting folate receptor-alpha (FRα) show potent anti-tumor activity against triple-negative breast cancer (TNBC). This novel immunotherapy approach holds promise for treating TNBC patients with limited options.
Area of Science:
- Immunology
- Oncology
- Cell Therapy
Background:
- Triple-negative breast cancer (TNBC) presents a poor prognosis due to a lack of specific therapeutic targets.
- Folate receptor-alpha (FRα) is emerging as a potential target for TNBC immunotherapy.
Purpose of the Study:
- To engineer gamma-delta T cells to express a chimeric antigen receptor (CAR) targeting FRα.
- To evaluate the anti-tumor efficacy of these engineered cells, secreting IL-7 and CCL19, against TNBC both in vitro and in vivo.
Main Methods:
- Gene modification of gamma-delta T cells to express FRα-specific CAR, IL-7, and CCL19 (7x19 CAR-γδT).
- In vitro assessment of anti-tumor activity.
- In vivo evaluation using a TNBC xenograft model, often in combination with peripheral blood mononuclear cells (PBMCs).
- Histopathological analysis of tumor tissues.
Main Results:
- 7x19 CAR-γδT cells demonstrated significant anti-tumor activity in vitro.
- Combined treatment with 7x19 CAR-γδT and PBMCs showed superior inhibition of TNBC xenograft growth compared to controls.
- Histological examination revealed increased infiltration of dendritic cells (DCs) and T cells within tumor tissues.
Conclusions:
- Engineered 7x19 CAR-γδT cells exhibit potent anti-TNBC activity.
- This approach shows broad application potential for treating patients with TNBC, a currently incurable breast cancer subtype.
