Mesothelin-targeted CAR T-cell therapy shows promise for malignant pleural disease
medwireNews: Phase I results reported at the AACR Annual Meeting 2019 in Atlanta, Georgia, USA, point to the potential of a chimeric antigen receptor (CAR) T-cell therapy directed against mesothelin in patients with malignant pleural disease.
Researcher Prasad Adusumilli (Memorial Sloan Kettering Cancer Center, New York, USA) said in a press release that “[t]reatment with CAR T cells results in dramatic successes in blood cancers; however, results have been disappointing to date for solid tumors.”
He continued: “The novelty of our study is that the CAR T cells target the cancer cell-surface protein, mesothelin, which is expressed on the majority of cancer cells, and they are delivered directly to the tumor site using regional delivery techniques.”
The study included 21 patients, 19 of whom had malignant pleural mesothelioma, while one patient each had pleural disease that had metastasized from lung and breast cancer. All participants received a single intrapleural dose of IcasM28z CAR T cells either with or without cyclophosphamide preconditioning.
Adusumilli noted that there was no evidence of toxicity related to CAR T-cell therapy of grade 3 or worse, and none of the patients experienced cytokine release syndrome or neurotoxicity. CAR T cell-related toxicity of grade 3 or worse, and none of the patients experienced cytokine release syndrome or neurotoxicity.
Treatment with mesothelin-targeted CAR T-cell therapy led to a complete metabolic response in two patients and a partial response in eight.
In light of preclinical research demonstrating reactivation of exhausted CAR T cells with the administration of PD-1 inhibitors in mouse models, the presenting author explained that 14 patients subsequently received anti-PD-1 therapy (1–21 doses).
Eleven of these patients were evaluable as they had received at least three doses of PD-1 inhibitor therapy and been followed up for at least 3 months. Two patients achieved complete metabolic responses that are ongoing after 60 and 22 weeks, respectively, while six participants had a partial response, giving a response rate of 72%.
“Combining rationally developed strategies – such as interventional radiology, T-cell genetic engineering, and newer immunotherapy agents – has produced encouraging results and provides rationale to further investigate this approach in aggressive, therapy-resistant cancers such as mesothelioma, for which the currently available treatment options are not optimal,” concluded Adusumilli.
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