CD47/SIRPα blocking enhances CD19/CD3-bispecific T cell engager antibody-mediated lysis of B cell malignancies.

Abstract:

:T cell immunotherapies are promising options in leukemia, among which the CD19/CD3-bispecific T cell engager antibody blinatumomab (MT103) has shown high response rates at very low doses in patients with lymphoma. However, the high CD47 expression in human lymphoma cells has limited the curative effects of blinatumomab other antibodies. Here we report the combined use of blinatumomab with a CD47-blocking antibody. CD47 antibodies preferentially enabled phagocytosis of non-Hodgkin lymphoma cells by both human and murine macrophages. Treatment of human non-Hodgkin lymphoma cell-engrafted mice with CD47 antibody and blinatumomab separately inhibited lymphoma partially, while combination treatment led to persistent control of lymphoma. These antibodies enhanced the therapeutic efficacy through mechanisms combining both innate and adaptive immune responses by induction of phagocytosis and T cell cytotoxicity. The combination strategy in this study might be applicable to many other cancers.

authors

Xu L,Wang S,Li J,Li B

doi

10.1016/j.bbrc.2018.12.175

subject

Has Abstract

pub_date

2019-02-12 00:00:00

pages

739-745

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(18)32862-6

journal_volume

509

pub_type

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