CAR T Cells Show Promise in Treating Mesothelioma and Pleural Malignancies

By Prasad S. Adusumilli, MD, FACS,

Prasad Adusumilli

The preliminary results of our ongoing trial investigating CAR T cell therapy to treat patients with malignant pleural disease show “encouraging clinical outcomes”.

Currently, 12 patients people with biopsy-proven malignant pleural disease expressing mesothelin (MSLN) are enrolled: two with secondary metastatic pleural disease from lung and breast cancer and ten with malignant pleural mesothelioma (MPM).

All 12 were given a single dose of IcasM28z chimeric antigen receptor (CAR) T cells intrapleurally.

Our initial results, which were reported at the American Society of Gene and Cell Therapy meeting this week, show that MSLN-targeted CAR T cells are well tolerated; have no sign of on-target, off-tumor, or therapy-related toxicity; and display evidence of CAR T cell antitumor activity.

Moreover, T cell persistence was associated with decreased soluble mesothelin-related peptide serum levels (more than 50 percent compared with pretreatment) and evidence of tumor regression on imaging studies (in five patients).

Our initial findings reveal that MSLN-targeted CAR T cells are well tolerated, with no evidence of on-target, off-tumor or therapy-related toxicity and with evidence of CAR T-cell antitumor activity.
Prasad S. Adusumilli
Prasad S. Adusumilli Deputy Chief, Thoracic Service; Co-Director, Mesothelioma Program; Head, Solid Tumors Cell Therapy, Cellular Therapeutics Center

One patient successfully underwent curative-intent surgical resection six weeks after CAR T cell infusion. CAR T cells were detected in the peripheral blood of six patients (day one to 31 weeks), as evidenced by vector copy number.

Once lack of toxicity had been established (at six to 17 weeks after CAR T cell infusion), seven patients received anti-PD-1 checkpoint blockade agents (in one to 10 cycles), off protocol and with no toxicity.

One patient with MPM had a complete metabolic response on a PET scan (having received 3E5 CAR T cells per kilogram and 10 cycles of anti-PD-1 therapy to date). This patient remains clinically well eight months after CAR T cell infusion, with evidence of CAR T cell persistence in peripheral blood and tissue at 31 weeks.

Our team at MSK developed CARs to target mesothelin, a cell-surface antigen that we have shown to be highly expressive of MPM; to be associated with invasion, matrix metallopeptidase (MMP)-9 secretion, and poor survival; and to have low expression in normal tissues.

We believe these initial results to be extremely promising as we continue to enroll patients in this trial.