Mesothelin-Targeted CARs: Driving T Cells to Solid Tumors.
Chimeric antigen receptors (CAR) are synthetic receptors that target T cells to cell-surface antigens and augment T-cell function and persistence. Mesothelin is a cell-surface antigen implicated in tumor invasion, which is highly expressed in mesothelioma and lung, pancreas, breast, ovarian, and other cancers. Its low-level expression in mesothelia, however, commands thoughtful therapeutic interventions. Encouragingly, recent clinical trials evaluating active immunization or immunoconjugates in patients with pancreatic adenocarcinoma or mesothelioma have shown responses without toxicity. Altogether, these findings and preclinical CAR therapy models using either systemic or regional T-cell delivery argue favorably for mesothelin CAR therapy in multiple solid tumors.


CONCLUSIONS
Recent success obtained with adoptive transfer of CAR T cells targeting CD19 in patients with refractory hematologic malignancies has generated much enthusiasm for T-cell engineering and raises the prospect of implementing similar strategies for solid tumors. Mesothelin is expressed in a wide range and a high percentage of solid tumors, which we review here in detail. Mesothelin CAR therapy has the potential to treat multiple solid malignancies.
Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, New York.
Aurore
A
Morello
Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, New York.
Michel
M
Sadelain
Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, New York. Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York. adusumip@mskcc.org.
Prasad S
PS
Adusumilli
D002986:Clinical Trials as Topic; D005260:Female; D058851:GPI-Linked Proteins / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D000090204:Mesothelin; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology*
C000605956:CD19-specific chimeric antigen receptor; D058851:GPI-Linked Proteins; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D000090204:Mesothelin