24 June 2022

Scientists have harnessed an immunity boosting protein to increase the effectiveness of CAR-T cell therapy.

Dr John DiPersio of Washington University in St. Louis, USA, and colleagues looked at methods to improve outcomes of chimeric antigen receptor (CAR) T-cell therapy, a common treatment for blood cancers.

They write in Nature Communications that a significant proportion of patients experience “suboptimal CAR-T cell cytotoxicity” and disease relapse.

In tests on mice, the team measured the benefits of a modified version of IL-7 – a growth factor that encourages the development of white blood cells – given alongside CAR-T cells targeting the CD19 antigen.

This showed that this “long-acting form of recombinant human interleukin-7 can promote proliferation, persistence and cytotoxicity of human CAR-T cells,” they report, “resulting in long-term tumour-free survival”.

The technique represents a “clinic-ready adjuvant for improving suboptimal CAR-T cell activity,” they write.

A phase 1 clinical trial in humans is due to begin shortly, explains Dr DiPersio. He says: “Many researchers are trying different strategies to enhance the function of CAR-T cells in treating blood cancers.

“We’re interested in IL-7 because we know it is a major driver of T cell expansion. The body makes IL-7 naturally to ramp up the number of T cells when a person gets sick, for example.

“When we give a long-acting type of IL-7 to tumour-bearing immunodeficient mice soon after CAR-T cell treatment, we see a dramatic expansion of these CAR-T cells greater than ten-thousandfold compared to mice not receiving IL-7.

“These CAR-T cells also persist longer and show dramatically increased anti-tumour activity.”

Source: Kim MY, Jayasinghe R, Devenport JM, Ritchey JK, Rettig MP, O'Neal J, Staser KW, Kennerly KM, Carter AJ, Gao F, Lee BH, Cooper ML, DiPersio JF. (2022) “A long-acting interleukin-7, rhIL-7-hyFc, enhances CAR-T cells expansion, persistence and anti-tumor activity.” Nature Communications, doi: 10.1038/s41467-022-30860-0

Link: https://www.nature.com/articles/s41467-022-30860-0

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