Poster Presentation CD1-MR1 Workshop 2025

Allogeneic NKT Cells Expressing a CD19-specific CAR in Patients with Relapsed or Refractory B cell Malignancies: an Interim Analysis (#130)

Leonid Metelitsa 1 2 3 , Amy N Courtney 2 , Carlos Ramos 3 , David Steffin 2 3 , Akshaya Adaikkalavan 2 , Claudia Martinez Amador 2 , Mahshid Azamian 3 , Helen E Heslop 3
  1. Baylor College of Medicine, Houston, TEXAS, United States
  2. Center for Advanced Innate Cell Therapy, Texas Children's Cancer and Hematology Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
  3. Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, TX, USA

Autologous T cells expressing CD19-specific chimeric antigen receptors (CARs) mediate high complete response rates in patients with B-cell malignancies. However, autologous cell products are costly, time-consuming to produce and demonstrate variable potency. CD1d-restricted Vα24-invariant natural killer T cells (NKTs) are not alloreactive and thus allogeneic NKTs can be used without risk of graft-versus-host disease. We generated five lots of healthy donor NKTs that co-express CD19-CAR, IL-15, and shRNA targeting beta-2-microglobulin and CD74 to downregulate HLA expression. Each lot averaged 14.8 ± 2.5 days in culture, and yielded 1.18 - 2.27x1010 cells with an NKT purity of 98.99% ± 1.02%. We are assessing the safety, persistence, and efficacy of this allogeneic product in ANCHOR (NCT00840853), a phase 1 dose-escalation trial for patients with relapsed/refractory B cell non-Hodgkin's lymphoma (NHL) and relapsed acute B lymphoblastic leukemia (ALL). Nine NHL patients have been infused on three dose levels (1x107 (DL1), 3x107(DL2), and 1x108 (DL3) CAR-NKT cells/m2) and three ALL patients have been infused on DL1. No dose-limiting toxicities related to CAR-NKTs have been observed.  Two cases of grade 2 or lower CRS have been observed and one case of grade 3 neurotoxicity, but all resolved quickly. Four out of nine NHL patients achieved a partial response four-to-six weeks after infusion that in two cases evolved into a complete response (CR) by three months post-infusion. Additionally, two out of three ALL patients achieved objective responses. We detected CAR-NKTs in the peripheral blood of some DL2 and DL3 patients, which peaked one week post-infusion and in biopsied tumor tissue from patients at one week and five weeks post-infusion. 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. Thus, NKTs represent a promising platform for “off-the-shelf” cancer immunotherapy.