SBIR Phase I: Generation of directly active monoclonal antibodies to CD19 for the treatment of B-cell malignancies

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The broader impact /commercial potential of this Small Business Innovation Research (SBIR) Phase I project relates to novel monoclonal antibody (mAb) therapies for the treatment of B-cell cancers (leukemias and lymphomas). Current drugs for these cancers cause severe side effects, and patients overwhelmingly relapse. The reagents proposed here could be the first mAbs to directly induce potent therapeutic effect in these diseases and are designed to be more tumor-specific than current therapies. Thus, the reagents offer the potential of a cure while minimizing the likelihood of side effects. Well-tolerated and effective therapeutics are a known unmet need for these malignancies. Additionally, these directly active mAbs could provide more affordable options than the engineered antibodies that have recently been approved. Research on these mAbs will elucidate the relationship between structural elements of receptors and their function. The success of these mAbs will validate a novel drug-target discovery platform, which will be applied in developing antibodies to treat other cancers and autoimmune diseases. This Small Business Innovation Research (SBIR) Phase I project applies a drug discovery platform, focused on developing mAbs to membrane receptors responsible for driving oncogenic signaling and malignant phenotypes. These novel antibodies may induce direct biologic effects by interrupting cell-growth/survival pathways. One of the key players in controlling multiple activation pathways involved in cell survival and proliferation is CD19, which is ubiquitously expressed on B-cells and its dysregulation leads to B-cell malignancies. Though CD19 has been used as a B-cell-specific drug target, no therapies exist that directly impact the signaling function of this receptor. This work has the potential to generate mAbs to two selected epitopes on CD19. mAbs that are specific and directly active will be further developed for clinical use.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.