• Science Saturday: Addressing the challenges of chimeric antigen receptor-T cell therapy

a medical illustation of chimeric antigen receptor-T (CAR-T) cell therapy

Chimeric antigen receptor-T cell therapy (CAR-T cell therapy) — a type of immunotherapy that reprograms a patient's T cells to recognize and destroy cancer cells — has revolutionized the treatment of blood cancers. While the technique has successfully sent patients with advanced disease into remission, it is far from perfect. CAR-T cell therapy has three main problems that Mayo is seeking to address to bring the full potential of this promising treatment to patients, says Saad Kenderian, M.B., Ch.B., a Mayo Clinic researcher.

The first problem is toxicity. In amping up the immune system to fight cancer, the technique can unleash a torrent of pro-inflammatory cytokines known as a "cytokine storm" that can be toxic to the brain, and lead to headache, confusion and delirium, among other neural changes. Fortunately, these changes are usually reversible.

The second problem — and the focus of Dr. Kenderian's research — is that CAR-T cell therapy only achieves long-lasting results in a small subset of patients.

For example, clinical trials have shown that a single infusion of CAR-T cell therapy targeted against a molecule known as BCMA that marks multiple myeloma cells prompted remission in 80%–100% of patients.

 "But most of those patients relapsed within two years, as the CAR-T cells became dysfunctional," says Dr. Kenderian.

He hypothesized that this dysfunction was caused by the tumor microenvironment. Kenderian's laboratory discovered that specific cells in the microenvironment — known as cancer-associated fibroblasts — exuded chemicals that kept the CAR-T cells from doing their jobs. Dr. Kenderian believed that if they could get rid of those cells, then the CAR-T cells could get back to fighting cancer.

Read the rest of the article on the Mayo Clinic Center for Regenerative Medicine blog.


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