Abstract
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.
Original language | English |
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Article number | e1386361 |
Number of pages | 8 |
Journal | OncoImmunology |
Volume | 7 |
Issue number | 2 |
DOIs | |
Publication status | Published - 2018 |
Keywords
- bispecific antibody
- CD47
- phagocytosis
- rituximab
- SIRP
- STEM-CELLS
- PHAGOCYTOSIS
- TARGET
- SELECTIVITY
- LYMPHOMA
- BLOCKADE
- PROTEIN
- TUMORS
- ALPHA