Early experiments suggest modified IL-7 may be able to boost CAR-T cell therapy

July 2022 Science Nalinee Pathak

Researchers from Washington University in St. Louis, USA report a modified form of interleukin-7 (IL-7) that can effectively enhance the efficacy of CAR-T cell therapy. The details of this protein and its mechanism of action were published in the reputed journal Nature communications.

The researchers describe the immune-stimulating capacity of a recombinant form of human IL-7 fused with hybrid Fc (rhIL-7-hyFc) to CAR T cells as a treatment enhancer for blood cancers. This compound has recently received FDA approval for the treatment of brain cancers (glioblastoma).

The team performed its pre-clinical experiments on mouse models. The team used the modified version of IL-7 and measured the benefits of CAR-T cell activity. They found that the modified IL-7 encourages the development of white blood cells. Moreover, it promotes proliferation, persistence and cytotoxicity of human CAR-T cells. This further led to an increase in the long-term tumour-free survival of the experimental animal.

Phase-I study

Based on the encouraging results of the experimental studies on mice, a Phase-I study on humans is being planned. The primary objective of the initial studies in humans is to examine the treatment-related toxicity and feasibility of the treatment. Therefore, according to FDA’s mandate, the drug will be tested after the CAR-T cell infusion to reduce any treatment-related toxicities.

Dr Joh DiPersio, the corresponding author of the publication said, “When we give a long-acting type of IL-7 to tumour-bearing immune-deficient mice soon after CAR-T cell treatment, we see a dramatic expansion of these CAR-T cells greater than ten-thousand fold compared to mice not receiving IL-7. These CAR-T cells also persist longer and show dramatically increased anti-tumour activity.”

Reference

Kim MY, Jayasinghe R, Devenport JM, Ritchey JK, et al. (2022) “A long-acting interleukin-7, rhIL-7-hyFc, enhances CAR-T cells expansion, persistence and anti-tumour activity.” Nature Communications.

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