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Updated: Jun 10, 2026
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Published on: May 9, 2025
p40-engineered CAR T-cells targeting CD276 enhance anti-tumor efficacy in non-small cell lung cancer
1Outpatient Department, Affiliated Hospital of Shaoxing University, Shaoxing, China.
Background:
Chimeric antigen receptor (CAR) T-cells have shown remarkable therapeutic efficacy in hematological malignancies; however, effective breakthroughs in solid tumors have not yet been achieved.
Objectives:
This study aimed to explore the therapeutic potential of p40-engineered CAR T-cells targeting CD276 (p40-H3BBz) for the treatment of non-small cell lung cancer (NSCLC).
Methods:
A CAR targeting CD276 (H3BBz) was engineered to co-express the p40 subunit via lentiviral transduction. The function of p40-H3BBz was evaluated by measuring cytokine secretion levels and performing luciferase-based cytotoxicity assays in vitro. In vivo efficacy was assessed using tumor-bearing mouse models, and T-cell infiltration was analyzed by immunohistochemistry.
Results:
The transduction efficiencies of H3BBz and p40-H3BBz were 63.7% and 52.3%, respectively, with both populations predominantly composed of CD4+ T-cells. Upon activation, p40-H3BBz exhibited increased IL-23 secretion, while IL-12 levels were comparable to those of H3BBz in vitro. p40-H3BBz also demonstrated enhanced cytotoxicity, degranulation, and increased production of IL-23 and IFN-γ. In vivo, p40-H3BBz CAR T-cells showed superior tumor growth inhibition, increased T-cell infiltration, and elevated IL-23 levels within tumors, without inducing significant toxicity in major organs.
Conclusion:
p40-H3BBz exhibits enhanced cytokine release and cytotoxic activity, representing a promising and safe therapeutic strategy for the treatment of NSCLC.
Insights
Engineered CAR T-cells targeting CD276 show promise for non-small cell lung cancer (NSCLC). The p40-H3BBz CAR T-cells demonstrated enhanced anti-tumor activity and T-cell infiltration in vivo.
Area of Science:
- Immunotherapy
- Oncology
- Cellular Therapy
Background:
- Chimeric antigen receptor (CAR) T-cell therapy is effective against blood cancers but faces challenges in solid tumors.
- Targeting solid tumors with CAR T-cells requires novel engineering strategies.
Purpose of the Study:
- To evaluate the therapeutic potential of p40-engineered CAR T-cells (p40-H3BBz) against CD276 in non-small cell lung cancer (NSCLC).
Main Methods:
- Engineered CAR T-cells (p40-H3BBz) targeting CD276 via lentiviral transduction.
- In vitro assessment of cytokine secretion and cytotoxicity.
- In vivo efficacy evaluation in NSCLC mouse models with immunohistochemical analysis of T-cell infiltration.
Main Results:
- p40-H3BBz CAR T-cells showed enhanced IL-23 secretion, cytotoxicity, and IFN-γ production in vitro.
- In vivo studies demonstrated superior tumor growth inhibition, increased T-cell infiltration, and elevated intratumoral IL-23.
- No significant toxicity was observed in major organs.
Conclusions:
- p40-H3BBz CAR T-cells exhibit potent anti-tumor activity and cytokine release, offering a promising and safe therapeutic approach for NSCLC.
- This engineered CAR T-cell strategy warrants further investigation for solid tumor treatment.
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