Initial Characterization of Nexi-001, a Donor-Derived T-Cell Product, for the Treatment AML Patients That Have Relapsed after Allogeneic Hematopoietic Stem Cell Transplant

Efficient ex-vivo generation of non-genetically engineered tumor-specific T cells remains a significant hurdle for the broad application of adoptive cell transfer (ACT) protocols for the treatment of cancer. Here, we describe the use of a novel AIM nanoparticle-based platform for generating multi-antigen tumor-specific T cells, which is used for the manufacture of our NEXI-001 clinical T cell product. The AIM nanoparticle (np) consists of a paramagnetic core, to which humanized HLA-A2-Ig dimer-molecules and anti-CD28 antibodies are conjugated. AIM np can be loaded with HLA-A2 restricted peptides of choice to create a disease relevant mix and used to enrich and expand tumor-specific CD8+ T cells. Using peptide loaded AIM np, we have developed a fully enclosed semi-automated, GMP T cell expansion platform that consistently generates clinically relevant numbers of tumor-specific, memory CD8+ T cells in 14 days, thus obviating the need for dendritic cell-based T cell expansion.

NEXI-001 is a T cell product consisting of >90% CD8+ T cells that recognize five specific HLA 02.01-restricted peptides from the WT1_, PRAME_, and Cyclin A1 antigens, each of which is commonly over-expressed on AML blasts and leukemic stem cells. The AIM manufacturing process is optimized to consistently produce cellular products that contain T cell memory subtypes that have been associated with anti-tumor potency and long-term persistence. Each NEXI-001 product is comprised of >95% memory T cells and include stem-like central memory (Tscm), central memory (Tcm) and effector memory (Tem) cells – those T cell subtypes with potential to provide long lasting graft vs leukemia (GVL) effects. Importantly, each product also contains very low proportions of naïve T cells with allo-reactive potential (Tn), which may further reduce the risk of GVHD. Here we present manufacturing data from the first 8 NEXI-001 products that were derived from allogeneic HSCT donors and infused in AML patients who had relapsed after allogeneic HSCT. This includes product release data and additional functional data that further characterize the quality of the T cell product. These data also demonstrate the capability of the manufacturing platform to consistently achieve important attributes while allowing for a wide range of incoming cell numbers and composition.

In summary, we have developed a novel AIM np-based T cell expansion platform for the rapid, streamlined generation of clinically relevant number of tumor-specific, multi-antigen, memory CD8+ T cells in 14 days. The results reported here support the development of additional multi-institution phase 1 /2 clinical trials of adoptive T cell transfer in hematologic and solid cancers.