Researchers at St. Jude found that animals lacking Tim4 resist the growth of B16 melanoma and Lewis lung carcinoma. Both Tim4 and LAP are involved in clearance of dying cells and studies on LC3-Associated Phagocytosis (LAP) suggest that this is due to enhanced T cell immunity to the cancer. So the researchers generated antibodies that neutralize Tim4 on the surface of myeloid cells for screening. These novel compositions and methods for blocking T cell immunoglobulin domain and mucin domain protein-4 (Tim4) on the surface of myeloid cells are to treat and prevent cancer. Blocking Tim4 on the surface of myeloid cells can restore anti-tumor immunity and reduce the uptake of apoptotic cells. Further, by administering an anti-Tim4 antibody, the pro-inflammatory anti-tumor response can be increased.
They also have methods for reducing the uptake of apoptotic cells and methods for increasing anti-tumor immunity and a method for producing monoclonal antibodies that bind Tim4 on the surface of myeloid cells. The anti-Tim4 antibodies can further be selected for their ability to inhibit engulfment of dead or dying cells, to elicit the production of inflammatory cytokines, and to restrict the growth of tumors.
Tim4, B16 melanoma, Lewis lung carcinoma, LC3-Associated Phagocytosis (LAP), T cell immunity, cancer, antibodies, myeloid cells, anti-tumor immunity, monoclonal antibodies, myeloid cells, inflammatory cytokines, tumors
Granted Patents or Published Applications
International Application published Oct. 2019 as WO 2019/197988 A1
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