OncoImmunology (Feb 2018)

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

  • Peter E. van Bommel,
  • Yuan He,
  • Ilona Schepel,
  • Mark A. J. M. Hendriks,
  • Valerie R. Wiersma,
  • Robert J. van Ginkel,
  • Tom van Meerten,
  • Emanuele Ammatuna,
  • Gerwin Huls,
  • Douwe F. Samplonius,
  • Wijnand Helfrich,
  • Edwin Bremer

DOI
https://doi.org/10.1080/2162402X.2017.1386361
Journal volume & issue
Vol. 7, no. 2

Abstract

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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.

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