Dual targeted CAR T-cell approach shows promise of reducing resistant relapse

The diagram above represents the process of chimeric antigen receptor T-cell therapy (CAR).
Image credit – Reyasingh56 via Wikipedia Creative Commons license.

CANCER DIGEST – April 10, 2021 – Early results from a small clinical trial involving 5 patients to test safety of a dual targeted immunotherapy approach has shown promise of minimizing treatment resistance, a group of UCLA Jonsson Comprehensive Cancer Center researchers report.
The new approach was presented at the American Association for Cancer Research virtual annual meeting April 10-15, 2021. It aims to avoid relapse by targeting two genes CD-19 and CD-20 that are key to B-cell lymphoma.

"One of the reasons CAR T-cell therapy can stop working in patients is because the cancer cells escape from therapy by losing the antigen CD19, which is what the CAR T-cells are engineered to target," principal investigator Sarah Larson, MD, explained in a press release. "One way to keep the CAR T-cells working is to have more than one antigen to target. So by using both CD19 and CD20, the thought is that it will be more effective and prevent the loss of the antigen, which is known as antigen escape, one of the common mechanisms of resistance."

The patients in the early trial all had measurable disease after undergoing two or more types of therapy for three types of non-Hodgkin lymphoma, a cancer or the lymphocytes of the immune system. Each patient was positive for CD-19 and CD-20 mutations. Each patient underwent chimeric antigen receptor T-cell (CAR T-cell) therapy that involves removing T-cells from the patients blood, modifying them to attack cells with the CD-19/CD-20 mutations.

The modified T-cells are then grown into billions of copies in the laboratory and then re-infused into the patients. The goal of the study was to determine a safe dose, but the researchers found that four of the five patients achieved a complete metabolic response, meaning all traces of the cancer were gone.

However what happens in about 50 percent of patients treated with such CAR T-cell therapy is relapse. The cancer returns and is resistant to the therapy. In this study, however, the duration of the response, meaning the time the patient is cancer free until the cancer re-emerges has not been reached after 13 months of follow up in four of the patients. The fifth patient did not respond to the therapy initially and cancer progression resumed 14 days after the CAR T-cell infusion.

While these findings are encouraging, the team notes the need to continue the next phase of the trial to test different doses on patients with more subtypes of the B-cell lymphoma.

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Sources: American Association for Cancer Research press release