| Autor: |
van Bommel, Peter E., He, Yuan, Schepel, Ilona, Hendriks, Mark A. J. M., Wiersma, Valerie R., van Ginkel, Robert J., van Meerten, Tom, Ammatuna, Emanuele, Huls, Gerwin, Samplonius, Douwe F., Helfrich, Wijnand, Bremer, Edwin |
| Předmět: |
|
| Zdroj: |
OncoImmunology; 2018, Vol. 7 Issue 2, pN.PAG-N.PAG, 1p |
| Abstrakt: |
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/CD47posmalignant B-cells, but not of CD20neg/CD47poscells, 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/CD47poscells and enhances the activity of therapeutic anticancer antibodies directed to B-cell malignancies. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
