Chimeric Antigen Receptor (CAR) T Cell Therapy for Malignant Pleural Mesothelioma (MPM)

Abstract

Cancer immunotherapy has now become a recognized approach to treating cancers. In addition to checkpoint blockade, adoptive T cell transfer (ACT) using chimeric antigen receptors (CARs) has shown impressive clinical outcomes in leukemias and is now being explored in solid tumors. CARs are engineered receptors, stably or transiently transduced into T cells, that aim to enhance T cell effector function by recognizing and binding to a specific tumor-associated antigen. In this review, we provide a summary of CAR T cell preclinical studies and clinical trials for malignant pleural mesothelioma (MPM), a rare, locally invasive pleural cancer with poor prognosis. We list other attractive potential targets for CAR T cell therapy for MPM, and discuss augmentation strategies of CAR T cell therapy with other forms of immunotherapy in this disease.

Keywords: adoptive cell transfer; chimeric antigen receptor T cells; immunotherapy; mesothelioma.

Figure 1

Chimeric antigen receptor (CAR) T cell. The single chain scFv—derived from the antigen-binding domain of antibodies—is fused to the CD3ζ transmembrane and intracellular signaling domains from the T-cell receptor complex; this is the first-generation CAR. Additional intracellular signaling domains are added for costimulatory signals, such as the CD28 and 4-1BB signaling domains, to yield second- and third-generation CARs.

Figure 2

Fibroblast Activation Protein Staining in two malignant pleural mesotheliomas (MPMs). Two MPM paraffin-embedded samples were stained with an anti-FAP antibody (Abcam antibody #207178 (monoclonal rabbit IgG), 1:250 dilution) or an isotype control. Strong stromal staining (brown) is seen in both samples. (All micrographs at 10× magnification).