Allogeneic natural killer T-cells (NKTs) expressing CD19-specific chimeric antigen receptors (CARs) are well tolerated and can mediate objective responses in non-Hodgkin lymphoma (NHL) and relapsed acute B-cell acute lymphoblastic leukemia (ALL) patients who relapsed following multiple salvage protocols, including commercial CAR-T products, according to a poster presentation presented at the 2025 Society for Immunotherapy of Cancer (SITC) Annual Meeting.
The researchers generated a bank of healthy donor NKTs that co-express a CD19-specific CAR, IL-15, and shRNA targeting beta-2-microglobulin and CD74 to downregulate HLA class I and II expression, respectively. They then assessed the safety, persistence, and efficacy of these allogeneic CD19-CAR-NKTs in ANCHOR, a first-in-human phase 1 dose-escalation trial for patients with relapsed or refractory B-cell NHL and relapsed ALL.
No dose-limiting toxicities related to CAR-NKTs were observed. Two cases of grade 2 or lower CRS and one case of grade 3 neurotoxicity were observed, but in all instances resolved quickly. Four out of nine patients with NHL achieved an initial partial response four-to-six weeks after infusion that in two cases evolved into a complete response by three months post-infusion. Additionally, two out of three patients with ALL achieved an objective response.
The authors noted that whereas autologous cell products are costly and time-consuming to produce and demonstrate variability in potency and toxicity, monomorphic CD1d-restricted Vα24-invariant NKTs are not alloreactive like HLA-restricted T-cells and therefore can be made from allogeneic donors without risking graft-versus-host disease.
“Our data indicate that allogeneic CAR-NKTs are well tolerated and can mediate objective responses in NHL/ALL patients that relapsed following multiple salvage protocols, including commercial CAR-T products,” the authors wrote. “Thus, NKTs represent a promising platform for ‘off-the-shelf’ cancer immunotherapy.”
Reference
Courtney AN, Ramos C, Steffin D. A phase I clinical trial of allogeneic NKT cells expressing a CD19-specific CAR in patients with relapsed or refractory B cell malignancies: an interim analysis. Abstract #553. Presented at the 2025 Society for Immunotherapy of Cancer (SITC) Annual Meeting. November 5–9; National Harbor, MD.
