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UCLA Opens Clinical Trial of Bispecific CAR T-cell Therapy for Advanced Lymphoma, Leukemia

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The UCLA Jonsson Cancer Center has begun enrolling patients in its latest chimeric antigen receptor T-cell immunotherapy trial for patients with relapsed or refractory non-Hodgkin’s B-cell lymphoma or chronic lymphocytic leukemia.

The trial (NCT04007029) will enroll patients aged 18 to 70 years and will use a novel bispecific CAR that targets both the CD19 and CD20 antigens on the surface of cancer cells. Current FDA-approved CAR T-cell therapies (tisagenlecleucel, Kymriah, Novartis; and axicabtagene ciloleucel, Yescarta, Kite/Gilead) target only the CD19 antigen.

“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,” Sarah Larson, MD, a health sciences clinical instructor in hematology/oncology at UCLA Health and the principle investigator for the trial, said in a press release.

“One way to keep the CAR T-cells working is to have more than one antigen to target,” she added. “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 new clinical trial is based on successful preclinical studies led by Yvonne Chen, PhD, co-director of the Jonsson Cancer Center’s Tumor Immunology Program and a member of the UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research. Her group demonstrated the ability to attack two target antigens in mice using CAR T-cells engineered in her laboratory.

“Based on these results, we’re quite optimistic that the bispecific CAR can achieve therapeutic improvement over the single-input CD19 CAR that’s currently available,” Chen said in a press release.

The trial is a phase 1, first-in-human study designed to determine the treatment’s safety and optimal dose. The study is sponsored by the Jonsson Comprehensive Cancer Center in collaboration with the NCI and the Parker Institute for Cancer Immunotherapy.

Trial participants will receive an infusion of autologous CD19/CD20 CARs engineered in Chen’s laboratory at UCLA. This is a single-center study available only to patients who can receive treatment at Jonsson Cancer Center.

Providers with potentially eligible patients should contact Bruck Habtemariam at (310) 794-0242 or via email at BHabtemariam@mednet.ucla.edu.