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. Si...
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doaj-28534e798d5449938af49fe87651c6842020-11-25T03:33:05ZengTaylor & Francis GroupOncoImmunology2162-402X2018-02-017210.1080/2162402X.2017.13863611386361CD20-selective inhibition of CD47-SIRPα “don't eat me” signaling with a bispecific antibody-derivative enhances the anticancer activity of daratumumab, alemtuzumab and obinutuzumabPeter E. van Bommel0Yuan He1Ilona Schepel2Mark A. J. M. Hendriks3Valerie R. Wiersma4Robert J. van Ginkel5Tom van Meerten6Emanuele Ammatuna7Gerwin Huls8Douwe F. Samplonius9Wijnand Helfrich10Edwin Bremer11University of Groningen, University Medical Center Groningen (UMCG)University of Groningen, University Medical Center Groningen (UMCG)University of Groningen, University Medical Center Groningen (UMCG)University of Groningen, University Medical Center Groningen (UMCG)University of Groningen, University Medical Center Groningen (UMCG)University of Groningen, University Medical Center Groningen (UMCG)University of Groningen, University Medical Center Groningen (UMCG)University of Groningen, University Medical Center Groningen (UMCG)University of Groningen, University Medical Center Groningen (UMCG)University of Groningen, University Medical Center Groningen (UMCG)University of Groningen, University Medical Center Groningen (UMCG)University of Groningen, University Medical Center Groningen (UMCG)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.http://dx.doi.org/10.1080/2162402X.2017.1386361bispecific antibodycd47phagocytosisrituximabsirpα |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 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 OncoImmunology bispecific antibody cd47 phagocytosis rituximab sirpα |
author_facet |
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 |
author_sort |
Peter E. van Bommel |
title |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
Taylor & Francis Group |
series |
OncoImmunology |
issn |
2162-402X |
publishDate |
2018-02-01 |
description |
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. |
topic |
bispecific antibody cd47 phagocytosis rituximab sirpα |
url |
http://dx.doi.org/10.1080/2162402X.2017.1386361 |
work_keys_str_mv |
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1724564745631039488 |