CD20-selective inhibition of CD47-SIRPα "don't eat me" signaling with a bispecific antibody-derivative enhances the anticancer activity of daratumumab, alemtuzumab and obinutuzumab.
Here, we report on a novel bispecific antibody-derivative, designated RTX-CD47, with unique capacity for CD20-directed inhibition of CD47-SIRPα "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 CD20pos/CD47pos malignant B-cells, but not of CD20neg/CD47pos 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 CD20neg/CD47pos cells and enhances the activity of therapeutic anticancer antibodies directed to B-cell malignancies.
['van Bommel|Peter E|PE|', 'He|Yuan|Y|', 'Schepel|Ilona|I|', 'Hendriks|Mark A J M|MAJM|', 'Wiersma|Valerie R|VR|', 'van Ginkel|Robert J|RJ|', 'van Meerten|Tom|T|', 'Ammatuna|Emanuele|E|', 'Huls|Gerwin|G|', 'Samplonius|Douwe F|DF|', 'Helfrich|Wijnand|W|', 'Bremer|Edwin|E|']
rituximab CD47 SIRPα bispecific antibody phagocytosis