What question did this study set out to answer?

This research aims to identify a mechanism to mitigate pulmonary toxicity associated with MSLN-directed CAR-T cell therapy in ovarian cancer.

April 5, 2026Cancer Research

AQP3 NOT Gating Mitigates Pulmonary Toxicity of MSLN-Directed CAR-T Cells

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This research aims to identify a mechanism to mitigate pulmonary toxicity associated with MSLN-directed CAR-T cell therapy in ovarian cancer.
Conducted a phase I trial evaluating safety of MSLN-directed CAR-T cells in patients with solid tumors.
Utilized hMSLN knock-in NCG mice with SKOV3 xenografts to study toxicity.
Analyzed MSLN expression and CAR-T cell infiltration alongside lung injury assessments.
Applied single-cell transcriptomic analyses on ovarian cancer and healthy lung tissues to identify safety strategies.
Developed dual-input MSLN/AQP3 lung-SAFE CAR-T cells and tested their efficacy against ovarian cancer cells.
Two patients in the trial experienced fatal pulmonary toxicity after MSLN-CAR-T cell infusion.
Generated hMSLN knock-in NCG mice showed similar lethal pulmonary injury observed in patients.
Identification of AQP3 provided a selective target to suppress CAR-T cell activation in the lungs without losing efficacy against ovarian cancer.

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Implication

Phase I trial reveals AQP3 as a key target to reduce lethal pulmonary toxicity in ovarian cancer treatments, suggesting safer CAR-T cell therapy options.

Cite This Study

Xiang et al. (2026) studied this question.

synapsesocial.com/papers/69d1fca7a79560c99a0a255a https://doi.org/10.1158/1538-7445.am2026-4277

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Implication

Phase I trial reveals AQP3 as a key target to reduce lethal pulmonary toxicity in ovarian cancer treatments, suggesting safer CAR-T cell therapy options.

AQP3 NOT Gating Mitigates Pulmonary Toxicity of MSLN-Directed CAR-T Cells

Key Points

Discussion

Implication

Cite This Study

AQP3 NOT Gating Mitigates Pulmonary Toxicity of MSLN-Directed CAR-T Cells

Key Points

Discussion

Implication

Cite This Study

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