SBIR Phase I: Antibody Therapy that Targets Neoantigens in Acute Myeloid Leukemia via the Antibody Dependent Cell-mediated Cytotoxicity Mechanism of Natural Killer Cells

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The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project focuses on the unique combination of cancer-specific antibodies and adoptive Natural Killer (NK) immune cells needed to offer personalizable cancer therapies. This innovation represents a platform technology that can spawn multiple innovative cancer treatments, which could positively impact life sciences innovation and, more importantly, advance the health and welfare of the global cancer population. This novel approach to immunotherapy of cancer is expected to be highly efficacious and, due to the specificity of its mechanism of action, virtually devoid of toxicity. This is significant in light of the fact that the national cost of cancer care is in the $200 billion range.This project seeks to provide a unique combination of cancer-specific antibodies and adoptive Natural Killer (NK) immune cells that synergize to achieve high efficacy, avoid toxicity to healthy cells, and offer a scalable, resource-efficient and personalizable therapy for cancer. The project focus is antibody targeting of a neoantigen found exclusively in diseased Acute Myeloid Leukemia (AML) cancer cells, in order to develop an effective treatment for relapsed / refractory disease. The 30-50 candidate antibodies will be generated and tested by first immunizing rats, isolating the resulting antigen-specific B cells using a specialized fluorescence-activated cell sorting technique, sequencing and cloning the antibody genes, and expressing the antibodies in producer cells. Candidate antibodies will be tested for specificity (enzyme-linked immunosorbent assay) and binding strength (surface plasmon resonance) for the neoantigen target, whittling down the list to ~15 candidate antibodies. Further screening will be achieved by evaluating antibody induction of AML cell-specific killing by NK cells; readouts will include AML target cell death measured by flow cytometry and lactate dehydrogenase release, degranulation by NK cells (indicating killing activity), and cytokine release. The top-performing 3-5 candidates will eventually be selected for preclinical testing.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.