Claudin-specific CAR T cells Evaluated in Gastric, and Pancreatic Cancer

CAR-T cell therapy appears to generate some response in advanced gastric and pancreatic cancer.

by Dr. C.H. Weaver M.D. 7/2019

One-third of a small cohort of patients with advanced gastric or pancreatic adenocarcinoma achieved objective responses to treatment with a novel claudin 18.2-specific chimeric antigen receptor T-cell therapy, according to results of a single-arm, phase 1 trial. (1)

CAR therapies utilize T-cells (CAR-T), a patient’s own immune cells that are re-programmed to recognize and kill cancer cells throughout the body. The process involves the removal of some T cells from a patient, and through laboratory processes, these T cells are re-programmed to identify a patient’s cancer cells.

Once the T cells have been programmed to identify a patient’s cancer cells, they are replicated in the laboratory, and infused back into the patient. These re-programmed T cells circulate throughout the body, identifying the cancer cells and mounting an immune attack against them. Simultaneously, the T cells are replicating within the body, so that more of the immune cells can identify and attack the cancer cells. CAR-T cell therapy has proven to be an effective treatment for certain leukemias and lymphomas. (2)

CAR-CLDN18.2 (CARsgen Therapeutics) targets claudin 18.2, a stomach-specific isoform of claudin-18 that is highly expressed in gastric and pancreatic adenocarcinomas.

Li and colleagues conducted a first-in-human, open-label, single-arm, phase 1 clinical trial to evaluate autologous CAR-CLDN18.2 T cells in patients with advanced gastric or pancreatic cancer whose tumors expressed claudin 18.2.

The results of the first twelve patients with biopsy-confirmed claudin 18.2-positive disease were reported at the 2019 American Society of Clinical annual meeting. All patients had received at least one previous line of treatment.

At the time of reporting 11 patients had been treated with one to five cycles of CAR-CLDN18.2 T cells. Eight patients had evidence of cancer regression including one complete response and three partial responses. Five patients achieved stable disease, whereas two patients experienced disease progression.

All patients in the trial experienced treatment-related side effects including one patient who had to withdraw from the study. There were no treatment-related deaths or dose-limiting toxicities.

Four patients experienced grade 3and experienced cytokine release syndrome.

The study authors concluded that “Claudin 18.2 CAR T cells combined with preconditioning chemotherapy was well-tolerated in patients treated at the active dose for at least two cycles and may have therapeutic efficacy in patients with advanced gastric and pancreatic adenocarcinoma.”

References:

  1. Zhan X, et al. Abstract 2509. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.
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