What question did this study set out to answer?

To overcome solid tumor immunosuppression by engineering CAR T cells to locally secrete single-domain antibody fragments.

February 4, 2020Cancer Immunology ResearchOpen Access

Improved Antitumor Efficacy of Chimeric Antigen Receptor T Cells that Secrete Single-Domain Antibody Fragments

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To overcome solid tumor immunosuppression by engineering CAR T cells to locally secrete single-domain antibody fragments.
Engineered CAR T cells to secrete single-domain antibody fragments (VHH or nanobodies) targeting CD47, PD-L1, or CTLA-4.
Evaluated the therapeutic activity and local delivery safety of modified CAR T cells and VHH-Fc fusions in immunocompetent animal models.
Secretion of anti-CD47 VHH enhanced innate immune system engagement, facilitated epitope spreading, and improved antitumor responses while local delivery prevented systemic toxicity.
Secretion of anti-PD-L1 or anti-CTLA-4 nanobodies improved CAR T-cell persistence, demonstrating that multiplexed delivery of diverse single-domain modalities can tailor the local immune response.

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Implication

Preclinical study demonstrates enhanced solid tumor eradication by nanobody-secreting CAR T cells in immunocompetent animal models, suggesting a strategy to counter tumor immunosuppression.

Cite This Study

Xie et al. (2020) studied this question.

synapsesocial.com/papers/6a740b6c6d8fa102e0cdec5f https://doi.org/10.1158/2326-6066.cir-19-0734

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Implication

Preclinical study demonstrates enhanced solid tumor eradication by nanobody-secreting CAR T cells in immunocompetent animal models, suggesting a strategy to counter tumor immunosuppression.

Improved Antitumor Efficacy of Chimeric Antigen Receptor T Cells that Secrete Single-Domain Antibody Fragments

Key Points

Discussion

Implication

Cite This Study

Improved Antitumor Efficacy of Chimeric Antigen Receptor T Cells that Secrete Single-Domain Antibody Fragments

Key Points

Discussion

Implication

Cite This Study

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