High affinity CD16^v/v allogeneic NK cell therapy, AB-101, enhances antibody-mediated cytotoxicity in B-cell driven diseases.

Abstract

Allogeneic NK cell therapies offer a compelling alternative to T-cell based approaches for the treatment of autoimmune diseases, with advantages including potent effector function, a favorable safety profile, and off-the-shelf availability. AB-101 is a cord blood-derived, non-genetically modified, cryopreserved NK cell product manufactured at industrial scale using a 50L bioreactor process, yielding ≥110 billion cells per run. AB-101 expresses high levels of CD56 and CD16, including the high-affinity 158V/V variant, which enhances antibody-dependent cellular cytotoxicity (ADCC). Phenotypic and functional analyses confirm a consistent, activated NK cell profile across Good Manufacturing Practice (GMP) lots. AB-101 demonstrates robust ADCC activity against tumor cells in vitro in combination with B-cell targeting monoclonal antibodies (mAbs) and shows positive results when administered in combination with rituximab to patients with non-Hodgkin lymphoma, with maintenance of high CD16 expression on AB-101. In autoimmune models, endogenous NK cells exhibited impaired cytotoxicity, whereas AB-101, which demonstrated enhanced killing of B cells from patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) when paired with anti-CD20 or anti-CD19 mAbs, suggesting therapeutic potential for AB-101 in autoimmune diseases. Collectively, these findings support AB-101 as a highly scalable, well-tolerated immunotherapy with potential across indications as an ADCC-enhancer targeting pathogenic B cells.