What question did this study set out to answer?

Determine whether co-expression of a dominant-negative TGF-β receptor enhances the proliferation, persistence, and antitumor efficacy of PSMA-targeted CAR T cells in prostate cancer.

May 8, 2018Molecular TherapyOpen Access

Dominant-Negative TGF-β Receptor Enhances PSMA-Targeted Human CAR T Cell Proliferation And Augments Prostate Cancer Eradication

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Authors

CKChristopher C. KlossUniversity of Pennsylvania JLJi‐Hyun LeeGachon University AZAaron ZhangRegeneron (United States)

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Implication

Interventional study demonstrates that dominant-negative TGF-β receptor expression enhances PSMA CAR T cell proliferation and eradicates prostate cancer, indicating a promising therapeutic strategy.

Key Points

Determine whether co-expression of a dominant-negative TGF-β receptor enhances the proliferation, persistence, and antitumor efficacy of PSMA-targeted CAR T cells in prostate cancer.
Engineered human PSMA-directed CAR T cells to co-express a dominant-negative TGF-β receptor II (dnTGF-βRII) to block immunosuppressive TGF-β signaling.
Evaluated CAR T cell proliferation, cytokine secretion, exhaustion profiles, and tumor clearance in aggressive human prostate cancer mouse xenograft models, leading to a phase I clinical trial (NCT03089203).
Co-expression of dnTGF-βRII in PSMA CAR T cells increased lymphocyte proliferation, enhanced cytokine production, and conferred functional resistance to immune exhaustion.
Engineered CAR T cells maintained long-term in vivo persistence and achieved complete tumor eradication in aggressive human prostate cancer mouse models.

Cite This Study

Kloss et al. (2018) studied this question.

synapsesocial.com/papers/6a75c57e1eaff9cba916183a https://doi.org/10.1016/j.ymthe.2018.05.003

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Implication

Interventional study demonstrates that dominant-negative TGF-β receptor expression enhances PSMA CAR T cell proliferation and eradicates prostate cancer, indicating a promising therapeutic strategy.

Dominant-Negative TGF-β Receptor Enhances PSMA-Targeted Human CAR T Cell Proliferation And Augments Prostate Cancer Eradication

Discussion

Member takes

Implication

Key Points

Cite This Study

Dominant-Negative TGF-β Receptor Enhances PSMA-Targeted Human CAR T Cell Proliferation And Augments Prostate Cancer Eradication

Discussion

Member takes

Implication

Key Points

Cite This Study

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