Researchers seek to improve success of chimeric antigen receptor-T cell therapy in non-Hodgkin lymphoma

JACKSONVILLE, Fla. – A study published by researchers from the Mayo Clinic Cancer Center at Mayo Clinic in Florida and Case Western, Cleveland Medical Center, examines the reasons for decreased remission rates in patients with non-Hodgkin’s lymphoma treated with therapeutic T-cell chimeric antigen receptors (CAR-T cell therapy). The study is published in Cancer Discovery.

“CAR-T cell therapy is a promising treatment for non-Hodgkin’s lymphoma, especially for patients who have relapsed or those who have not responded to prior treatments,” says Tae Hyun Hwang, Ph.D., researcher at Mayo Clinic Cancer Center. in Jacksonville, Florida.

However, Dr. Hwang says recent long-term follow-up data suggests that the success rate of CAR-T cell therapy for patients with non-Hodgkin’s lymphoma may be declining. “Sustained remission in this setting ranges from 30% to 40%, so identifying a predictive biomarker to measure CAR-T cell resistance is essential so that we can better match patients to effective treatment,” says Dr Hwang.

“The overall goal of our research is to support precision cancer care. New therapeutic strategies will help us improve the effectiveness of CAR-T cell therapy for patients with non-Hodgkin’s lymphoma,” says David Wald, MD, Ph.D., of Case Western, Cleveland Medical Center, co-author of the study,

“Our team hypothesized that there would be distinct molecular patterns in CAR-T cells between patients who responded to treatment and patients who did not,” says Dr. Hwang. He says the team used innovative computational and experimental approaches to identify these patterns.

The researchers generated single-cell RNA and protein sequencing data for CAR-T cells before they were administered to patients and then repeatedly after they were infused into patients. Dr. Hwang says this work has generated more than 133,000 single-cell expression profiles that researchers have used to develop and apply computational approaches to dissect single-cell-level RNA or protein expression patterns of CAR-T cells. associated with response to treatment.

Using these computational approaches, the team found that a gene called TIGIT – a T cell – was highly expressed in post-infusion CAR-T cells from patients who failed to respond to CAR-T cell therapy. The team also validated that TIGIT drives CAR-T cell exhaustion and dysfunction, and they found that blocking TIGIT with CAR-T cell therapy could improve treatment efficacy in an in vivo study.

“If our results can be validated in prospective clinical trials, our TIGIT blocking strategy with CAR-T cell therapy could improve current responses of CAR-T cell therapy in patients with non-Hodgkin’s lymphoma and could also improve the patient survival,” says Dr. Hwang. .

/Public release, courtesy of Mayo Clinic. This material from the original organization/authors may be ad hoc in nature, edited for clarity, style and length. The views and opinions expressed are those of the author or authors. See in full here.

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