Autologous CAR-T therapies have dramatically improved outcomes in B cell malignancies but face limitations including high manufacturing costs, variable product quality, and production delays or failures. ALA-101 is an allogeneic, off-the-shelf CD19-targeted cell therapy based on invariant natural killer T (iNKT) cells. iNKT cells are uniquely suited for allogeneic use due to their MHC-independent recognition via CD1d and their ability to target tumor cells through both exogenous CAR and endogenous TCR/NKG2D-mediated mechanisms. ALA-101 is being developed to overcome current autologous CAR-T challenges while enhancing safety and tumor clearance.
ALA-101 is manufactured from healthy donor PBMCs using a proprietary, clinic-ready process involving iNKT enrichment, CAR transduction with a third-generation lentiviral vector, and robust expansion prior to cryopreservation. The process has been successfully scaled, achieving >5,000-fold expansion, >99% iNKT purity, a balanced CD4+/CD4– phenotype, and ~60% CAR transduction efficiency.
In vitro, CAR-iNKT cells showed rapid and potent cytotoxicity against CD19+ tumor cells. Subset analysis demonstrated that CD4– CAR-iNKT cells exhibited superior cytotoxicity, while CD4+ CAR-iNKT cells had enhanced proliferative capacity. ALA-101 provided a significantly survival benefit in an aggressive lymphoma xenograft model, with CAR-iNKT cells detected in blood, bone marrow, and brain up to 28 days post-infusion.
ALA-101 represents a next-generation allogeneic CAR-iNKT platform with dual-targeting capability, strong preclinical efficacy, and scalable manufacturing. A first-in-human, open-label Phase 1 clinical trial will assess safety, tolerability, dose-limiting toxicities, pharmacokinetics, and preliminary anti-tumor activity across escalating dose levels. This trial represents a critical advancement in harnessing the full therapeutic potential of CAR-iNKT cells, which offer distinct advantages over conventional CAR-T cell therapies—including innate anti-tumor activity, reduced risk of graft-versus-host disease, and off-the-shelf accessibility.