A newly identified immune checkpoint protein may lead to future cancer therapies

The effectiveness of CAR T cell therapyagainst a variety of cancers, including solid tumors, could be boosted greatly by using CRISPR-Cas9 technology to knock out the gene for CD5, a protein found on the surface of T cells, according to a preclinical study from investigators at the Perelman School of Medicineand Abramson Cancer Center.

CAR T cells are T cells that have been engineered to attack specific targets found on cancer cells. They have had remarkable results in some patients with blood cancers. But they have not performed well against other cancers including solid-tumor cancers, such as pancreatic cancer, prostate cancer, and melanoma. Researchers have been searching for techniques to boost the effectiveness of CAR T cell therapy.

The study, published in Science Immunology, suggests that knocking out CD5 could be a prime technique. Illuminating the protein's previously murky role, the researchers found that it works as a powerful immune checkpoint, reining in T cell effectiveness. Removing it, the researchers show, dramatically enhances CAR T cell anticancer activity in a variety of preclinical cancer models. Immune checkpoint mechanisms are regulatory switches that help keep immune responses from becoming too intense and causing collateral tissue damage. Cancers often hijack these mechanisms to suppress anticancer immune responses.

"We've discovered in preclinical models that CD5 deletion greatly enhances the function of CAR T cells against multiple cancers," says senior author Marco Ruella, an assistant professor of hematology-oncology, researcher with the Center for Cellular Immunotherapies, and the scientific director of Penn Medicine's Lymphoma Program. "The striking effects we observed across preclinical models suggest that CD5 knockout could be a general strategy for enhancing CAR T cell function."

Read more at Penn Medicine News.