What question did this study set out to answer?

To develop a modular, non-genetically engineered anti-mesothelin (MSLN) CAR-like natural killer cell therapy equipped with a tumor-penetrating peptide to overcome poor tumor targeting and infiltration.

December 23, 2025Signal Transduction and Targeted TherapyOpen Access

Anti-MSLN chimeric antigen receptor-like NK cell therapy with tumor-penetrating capacity (uCAR-like NK) for solid tumors

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To develop a modular, non-genetically engineered anti-mesothelin (MSLN) CAR-like natural killer cell therapy equipped with a tumor-penetrating peptide to overcome poor tumor targeting and infiltration.
Assembled a tetravalent bispecific cell engager targeting MSLN and CD16A using the SpyTag/SpyCatcher system.
Precomplexed cytokine-induced memory-like NK cells (activated with IL-12, IL-15, and IL-18) with the bispecific engager and the uCendR tumor-penetrating peptide to yield uCAR-like NK cells.
Assessed in vitro selective tumor lysis and evaluated in vivo intratumoral penetration and antitumor efficacy in MSLN-positive xenograft models.
Anti-MSLN CAR-like NK cells demonstrated selective cytotoxicity against MSLN-positive tumor cells in vitro while sparing MSLN-negative targets.
In MSLN-positive xenograft models, anti-MSLN CAR-like NK cells produced robust antitumor efficacy with favorable tolerability and no significant body weight loss or overt toxicity.
Incorporation of the uCendR peptide significantly enhanced intratumoral penetration and yielded superior tumor control compared to conventional CAR-like NK cells.

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Implication

Preclinical study demonstrates enhanced tumor penetration and antitumor efficacy of uCAR-like NK cells in mesothelin-positive solid tumors, highlighting a non-genetic immunotherapy platform.

Cite This Study

An et al. (2025) studied this question.

synapsesocial.com/papers/6a83ca6fa3cef8348e9971ec https://doi.org/10.1038/s41392-025-02524-0

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Implication

Preclinical study demonstrates enhanced tumor penetration and antitumor efficacy of uCAR-like NK cells in mesothelin-positive solid tumors, highlighting a non-genetic immunotherapy platform.

Anti-MSLN chimeric antigen receptor-like NK cell therapy with tumor-penetrating capacity (uCAR-like NK) for solid tumors

Key Points

Discussion

Implication

Cite This Study

Anti-MSLN chimeric antigen receptor-like NK cell therapy with tumor-penetrating capacity (uCAR-like NK) for solid tumors

Key Points

Discussion

Implication

Cite This Study

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