UCSF researchers have engineered a chimeric antigen receptor for phagocytosis (CAR-P) that promotes engulfment of cancer cells.
Approximately 143,000 new cases of leukemia and lymphoma will be diagnosed in the US in 2018, with about 44,000 patients dying from these diseases in this year. Current standards of treatment are chemotherapy and stem cell transplantation, but recently CAR-T therapies that utilize engineered T cells such as Kymriah and Yescarta have become available to treat some rare and persistent forms of leukemia. In addition to being effective in cases where traditional therapies have failed, these CAR-T therapies are promising due to their shorter duration of treatment and long-term efficacy over traditional treatments.
However, since T cells cannot readily penetrate solid tumors, these CAR-T therapies are unlikely to be effective in some forms of lymphoma. Macrophages however readily interact with the tumor microenvironment of solid tumors. CAR-P therapies therefore could help bypass this hurdle and provide additional treatment options that can work either alone or with existing treatments to improve patient survival.
ADVANTAGES OF TECHNOLOGY
Chimeric Antigen Receptors for Phagocytosis (CAR-P) consist of an extracellular antibody fragment specific against cancer antigens, a plasma membrane signal peptide and transmembrane domain, and the cytoplasmic domains of an engulfment receptor.
When expressed in macrophages, the extracellular antibody fragment recognizes and binds to specific cancer antigens. This leads to the phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs), which promotes either partial or whole cell phagocytosis of the bound target cell.
To develop & commercialize the technology for cancer therapeutics
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