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Ex vivo pleural effusion cultures to study chimeric antigen receptor T cell cytotoxicity in an immunocompetent environment.

ABSTRACT: Current in vitro and in vivo assays used to study immunotherapeutic interventions lack human immune components that mimic the tumor microenvironment to investigate drug potency and limitations of efficacy. Herein, we describe an ex vivo pleural effusion culture (ePEC) assay, using malignant pleural-effusion-derived soluble and cellular factors that differentially affected the cytotoxicity of chimeric antigen receptor (CAR) T cells. Following identification of CAR T cell-suppressive factors, blocking of individual factors reveals their contribution to compromising T cell efficacy. ePEC is a human component assay that can be utilized for developing next-generation cell and antibody therapies that counteract immunosuppression.

SUBMITTER: Tano ZE 

PROVIDER: S-EPMC10694486 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Ex vivo pleural effusion cultures to study chimeric antigen receptor T cell cytotoxicity in an immunocompetent environment.

Tano Zachary E ZE   Kiesgen Stefan S   Chintala Navin K NK   Dozier Jordan J   Quach Hue Tu HT   Messinger John J   Tan Kay See KS   Adusumilli Prasad S PS  

Cell reports methods 20231023 11

Current in vitro and in vivo assays used to study immunotherapeutic interventions lack human immune components that mimic the tumor microenvironment to investigate drug potency and limitations of efficacy. Herein, we describe an ex vivo pleural effusion culture (ePEC) assay, using malignant pleural-effusion-derived soluble and cellular factors that differentially affected the cytotoxicity of chimeric antigen receptor (CAR) T cells. Following identification of CAR T cell-suppressive factors, bloc  ...[more]

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