Research highlight

Cancer: CAR T therapy exhibits promising activity in gastrointestinal cancers

Nature Medicine

May 10, 2022

CAR T cell immunotherapy that specifically targets a protein that is highly expressed in gastrointestinal tumor cells (CLDN18.2) — is safe and elicits a response rate of 48.6% in patients with gastrointestinal cancers, and 57.1% in patients with gastric cancer, according to a paper published in Nature Medicine. These findings — revealed during the initial analysis of an ongoing phase 1 clinical trial — suggest that CLDN18.2-specific CAR T cell therapy may be a viable treatment option for patients with cancers of the digestive system.

Patients with gastrointestinal cancers — including gastric cancer and pancreatic cancer — generally have poor prognoses, with limited treatment options. CAR T cell therapy — an immunotherapy in which a patient’s T cells are modified so that they can recognize and kill cancer cells — is approved for the treatment of hematologic cancers, such as leukemia and lymphoma. However, CAR-T’s potential in treating solid tumors — such as gastrointestinal cancers — remains unclear due to difficulties in targeting these types of cancers.

Lin Shen and colleagues present initial analyses from an ongoing phase 1 clinical trial of CLDN18.2-targeting CAR T cells in patients with previously treated gastrointestinal cancers that express CLDN18.2 (37 patients in total; 28 with gastric cancer or adenocarcinoma of gastroesophageal junction, 5 with pancreatic cancer). Overall, an acceptable safety profile was observed following the first infusion of CAR T cells. The overall response rate and disease control rate were 48.6% and 73.0%, respectively, in all treated patients, and 57.1% and 75.0% in patients with gastric cancers.

These results provide new insights into CAR T cell implementation for the treatment of solid tumors. However, final results from this trial, along with follow up in large trials, are required.

doi: 10.1038/s41591-022-01800-8

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