About 89 percent of the patients that were diagnosed with lymphoma in 2015 had Non-Hodgkin’s lymphoma (NHL). NHLs are a heterogeneous group of lymphoproliferative tumors, which are mostly derived from B-lymphocytes. Several B-cell surface receptors such as CD19 and CD20 have been evaluated for developing immunotherapies for B-cell malignancies. The most prominent immunotherapeutic for NHL is rituximab, a chimeric monoclonal antibody that binds CD20. Successful clinical outcomes of B-cell NHL patients treated with antibody based immunotherapeutics such as Rituximab have confirmed the hypothesis that antibody-based therapies have significant advantages over traditional therapeutic regimens for treatment of lymphomas. Despite these promising results, a significant number of NHL patients develop resistance to therapy or relapse, implying that room for improvement remains.
In collaboration with Dr. Alan Epstein's research group at the USC Keck School of Medicine, our team has developed a project utilizing single chain variable fragment antibodies (scFv) in fusion with elastin-like polypeptide (ELP) protein-polymers. These fusions assemble multivalent nanoworms that target B-cell surface receptors. We recently demonstrated that one of these scFv-ELP nanoworms outperformed Rituximab in a disease model of lymphoma. We are currently optimizing this generality of this strategy and exploring other potential targets.
Selected Publication
A Hybrid Protein–Polymer Nanoworm Potentiates Apoptosis Better than a Monoclonal Antibody
Suhaas Rayudu Aluri, Pu Shi, Joshua A. Gustafson, Wan Wang, Yi-An Lin, Honggang Cui, Shuanglong Liu, Peter S. Conti, Zibo Li, Peisheng Hu, Alan L. Epstein, and John Andrew MacKay
ACS Nano. 2014 Mar 25;8(3):2064-76.
