期刊
ONCOIMMUNOLOGY
卷 7, 期 2, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2017.1386361
关键词
bispecific antibody; CD47; phagocytosis; rituximab; SIRP
资金
- Dutch Cancer Society [RUG 2009-4355, RUG2011-5206, RUG2012-5541, RUG2013-6209, RUG2014-6986]
Here, we report on a novel bispecific antibody-derivative, designated RTX-CD47, with unique capacity for CD20-directed inhibition of CD47-SIRP alpha don't eat me signaling. RTX-CD47 comprises a CD20-targeting scFv antibody fragment derived from rituximab fused in tandem to a CD47-blocking scFv. Single agent treatment with RTX-CD47 triggered significant phagocytic removal of CD20(pos)/CD47(pos) malignant B-cells, but not of CD20(neg)/CD47(pos) cells, and required no pro-phagocytic FcR-mediated signaling. Importantly, treatment with RTX-CD47 synergistically enhanced the phagocytic elimination of primary malignant B cells by autologous phagocytic effector cells as induced by therapeutic anticancer antibodies daratumumab (anti-CD38), alemtuzumab (anti-CD52) and obinutuzumab (anti-CD20). In conclusion, RTX-CD47 blocks CD47 don't eat me signaling by cancer cells in a CD20-directed manner with essentially no activity towards CD20(neg)/CD47(pos) cells and enhances the activity of therapeutic anticancer antibodies directed to B-cell malignancies.
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