Exciting New CAR T Cell Therapy Trial Opens at MSK

By Prasad S. Adusumilli, MD, FACS,

Friday, September 23, 2016

The Thoracic Surgery Service at Memorial Sloan Kettering Cancer Center (MSK) is excited to announce the opening of a new clinical trial that uses an adoptive T cell therapy approach to treat mesothelioma and metastatic lung and breast cancers.

The CAR T Cell Immunotherapy Breakthrough

Chimeric antigen receptor (CAR) T cell immunotherapy, a targeted therapy that genetically redirects the patient’s own T cells to lyse cancer cells, has achieved dramatic success in hematological malignancies. CARs are genetically engineered antigen-specific receptors that, when transduced into T cells, can specifically recognize and kill cancer cells. Groundbreaking MSK studies have shown complete remissions in patients with therapy-refractory lymphoma and leukemia (1).

Our thoracic cancer research team has identified mesothelin as an ideal target for cellular immunotherapy. Mesothelin is a cancer-cell surface antigen expressed in a majority of patients with mesothelioma, lung adenocarcinoma, and triple-negative breast cancer. Published studies from our laboratory have shown that mesothelin expression is associated with cancer cell aggressiveness. (2), (3), (4) Using clinically relevant mouse models, we have demonstrated the antitumor efficacy of mesothelin-targeted CAR T cells when injected directly into the pleural cavity. (5)

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MSK Phase I Trial Opens

On the basis of this solid preclinical data, we have opened a phase I clinical trial; three patients are already receiving treatment. Patients with primary mesothelioma or metastatic pleural disease from lung or breast cancers are eligible to join the study. The treatment involves harvesting the patient’s T cells from the peripheral blood, transducing the cells with mesothelin CARs, and expanding the quantity at our FDA-approved Cell Therapy and Cell Engineering Facility. The expanded mesothelin-targeted CAR T cells are then infused directly into the pleural cavity of the patient through PleurX catheters.

In contrast to other existing CAR T cell clinical trials, this trial uses a gene construct that is derived from all human components, which is expected to minimize the immune reaction. In addition, the T cells are engineered to include a genetic “safety switch” that, through the administration of the dimerizing agent AP1903, allows for the rapid elimination of the T cells in the event of unacceptable toxicity.

Patients will undergo the engineered T cell therapy only once. After treatment, they receive weekly follow-up for the first eight weeks, followed by monthly follow-up and then yearly follow-up for the remainder of their time on the trial.

For more information about this study and to inquire about eligibility, please contact Dr. Prasad Adusumilli at 212-639-8093.

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  1. Brentjens RJ, Davila ML, Riviere I, et al. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Science Transl Med 2013; 5(177):177ra138.

  2. Kachala SS, Bograd AJ, Villena-Vargas J, et al. Mesothelin overexpression is a marker of tumor aggressiveness and is associated with reduced recurrence-free and overall survival in early-stage lung adenocarcinoma. Clin Cancer Res 2014; 20(4):1020-8.

  3. Servais EL, Colovos C, Rodriguez LA, et al. Mesothelin overexpression promotes mesothelioma cell invasion and MMP-9 secretion in an orthotopic mouse model and in epithelioid pleural mesothelioma patients. Clin Cancer Res 2012; 18(9):2478-89.

  4. Tozbikian G, Brogi E, Kadota K, et al. Mesothelin expression in triple negative breast carcinomas correlates significantly with basal-like phenotype, distant metastases and decreased survival. PloS One 2014; 9(12):e114900.

  5. Adusumilli PS, Cherkassky L, Villena-Vargas J, et al. Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity. Science Transl Med 2014; 6(261):261ra151.