Stanford’s cancer researchers have powered several breakthroughs in chimeric antigen receptor (CAR)-T cell therapy. Recently, a new, innovative CAR-T therapy has shown promising, early results for treating a high-risk lymphoma population. These results were recently presented at the 2025 American Society of Clinical Oncology Annual Meeting and European Hematology Association Annual Meeting.
CAR-T therapy destroys cancer cells by engineering a patient’s own immune cells to target molecular markers, or antigens, on the cancer cells’ surface, making it easier for the immune cells to find the cancer. Typically, CAR-T therapies target one antigen, but the new treatment, KITE-363, targets two antigens named CD19 and CD20. Additionally, KITE-363 has two different costimulatory domains, which are the ‘engines’ that drive CAR-T cells to expand, or multiply, and to live for a long time in the patient.
Saurabh Dahiya, MD, FACP, principal investigator of the clinical trial, clinical director of Cancer Cell Therapy (CCT), and leader of the Stanford Cancer Institute CCT Clinical Research Group, says, “Dual targeting with two distinct CARs on one T-cell can potentially address tumor heterogeneity and improve treatment responses. Additionally, two costimulatory domains change how the CAR-T cell behaves in the patients, leading to more regulated, homeostatic CAR-T cell expansion.”
A phase 1, first-in-human, multicenter clinical trial enrolled 37 patients with B-cell lymphoma, the majority of whom had an aggressive subtype known as large B-cell lymphoma (LBCL). Half of the patients were either refractory, meaning their cancer didn’t respond to treatment, or relapsed, where their cancer initially went away after treatment and then returned. All patients had tumors positive for CD19 and/or CD20, with 78% being positive for both, and the trial had a median follow-up of 12 months.
Of the 26 patients who received the highest treatment dose, 87% responded and saw their cancer shrink. 78% of this group had their cancer disappear entirely, with 71% being cancer-free for six months or longer after treatment.
Dahiya says, “These are very high and unprecedented response rates in a high-risk and refractory patient population. KITE-363 may be a promising new treatment for people with B-cell lymphoma.”
Additionally, at its highest dose, KITE-363 expanded at a rate three to five times higher than seen with the previous generation of CAR-T therapies without an increase in side effects.
“Historically, higher CAR-T cell expansion has been related to higher toxicity, but we saw a decoupling of robust expansion from resulting toxicity and did not see a major increase in the toxicity profile.”
He describes the side effects as manageable, with most not being severe. At the highest dose level, patients did not have high-grade neurotoxicity, known as immune effector cell-associated neurotoxicity syndrome (ICANS). He notes that this is in sharp contrast with the FDA-approved CAR-T treatments that only target the CD19 antigen.
“There is a lot of excitement about this product. By expressing the two CARs in a one-to-one fashion, powering the product with the two costimulatory domains, and achieving a safe toxicity profile, we’ve achieved significant responses in high-risk lymphoma patients and given them a chance they may not have otherwise had. This treatment seems groundbreaking to me.”