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Bispecific hybrid nanoworms for immunotherapy of B-cell lymphoma

Nearly 72,000 cases of B-cell or non-Hodgkin’s lymphoma (NHL) are diagnosed each year, and almost 20,000 people die from the disease annually.

This project employs protein polymers to develop temperature-responsive nanoparticles that assemble from a fusion between a single-chain antibody and a soluble protein polymer. The team has demonstrated its strategy using the blockbuster drug rituximab — a chimeric antibody that targets CD20, a surface protein present in B cells. Although rituximab is now standard treatment for NHL, nanoworms that bind to CD20 dramatically outperform rituximab in killing tumor cells. Work in animal models has already demonstrated great potential for development of strategies that simultaneously diagnose, treat and monitor outcomes using nanoworm technology.

Next, the team is developing nanoworms that can bind to multiple target receptors, potentially crosslinking normal immune cells with cancer cells. When crosslinked, these immune cells actively kill cancer cells, which has led to the recent approval of biological drugs with a remarkable response rate among patients. This strategy has great potential, and scientists have only scratched the surface of optimizing these materials. The USC team’s work could eventually result in new classes of immunotherapies tailored to each patient.