Poster Presentation CD1-MR1 2024

Allogeneic NKT Cells Expressing a CD19-specific CAR in Patients with Relapsed or Refractory B cell Malignancies: an Interim Analysis (#203)

Amy N Courtney 1 , Carlos A Ramos 2 , Claudia M Amador 1 , Mahshid Azamian 2 , Leonid S Metelitsa 1 2
  1. Center for Advanced Innate Cell Therapy, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
  2. Center for Cell and Gene Therapy, Department of Medicine, Baylor College of Medicine, Houston, TX, USA

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 and time-consuming to produce and demonstrate variability in potency and toxicity. Monomorphic CD1d-restricted Vα24-invariant natural killer T cells (NKTs) are not alloreactive like HLA-restricted T cells and therefore can be made from allogeneic donors without risking graft-versus-host disease. We generated a bank of healthy donor NKTs that co-express a CD19-CAR, IL-15, and shRNA targeting beta-2-microglobulin and CD74 to downregulate HLA class I and II expression, respectively. Five lots of CAR-NKTs have been produced for this bank with each lot averaging 14.8 ± 2.5 days in culture, yielding 1.18 - 2.27x1010 cells per lot and an average NKT purity of 98.99% ± 1.02%. We are assessing the safety, persistence, and efficacy of this allogeneic product in ANCHOR, a first-in-human phase 1 dose-escalation trial for patients with relapsed/refractory B cell non-Hodgkin's lymphoma (NHL) and relapsed acute B lymphoblastic leukemia (ALL)(NCT00840853). No dose-limiting or grade 2+ toxicities related to CAR-NKTs have been observed. Seven NHL patients have been infused with CAR-NKTs so far at three dose levels (DL1:1x107, DL2:3x107, and DL3:1x108 CAR-NKT cells/m2), and three achieved objective responses including two complete responses. Additionally, one of two ALL patients treated on DL1 achieved a complete response. Though we did not detect CAR-NKTs in the peripheral blood of patients on DL1, we did find evidence of CAR-NKT proliferation that peaked one week after infusion in two NHL patients on DLs 2 and 3. CAR-NKTs were also found in tumor tissue from NHL patient biopsies at weeks one and five post-infusion. Our data indicate that allogeneic CAR-NKTs are well tolerated and can produce objective responses in relapsed/refractory NHL/ALL patients, suggesting that NKTs represent a promising platform for “off-the-shelf” cancer immunotherapy.