Complement in monoclonal antibody therapy of cancer.

Abstract:

:Monoclonal antibodies (mAb) have been used as targeted treatments against cancer for more than a decade, with mixed results. Research is needed to understand mAb mechanisms of action with the goal of improving the efficacy of currently used mAbs and guiding the design of novel mAbs. While some mAb-induced tumor cell killing is a result of direct effects on tumor cell signaling, mAb opsonization of tumor cells also triggers activation of immune responses due to complement activation and engagement of antibody receptors on immune effector cells. In fact, complement has been shown to play an important role in modulating the anti-tumor activity of many mAb through complement-dependent cytotoxicity, antibody-dependent cytotoxicity, and through indirect effects by modulating the tumor microenvironment. Complement activity can have both agonistic and antagonistic effects on these processes. How the balance of such effects impacts on the clinical efficacy of mAb therapy remains unclear. In this review, we discuss the mAbs currently approved for cancer treatment and examine how complement can impact their efficacy with a focus on how this information might be used to improve the clinical efficacy of mAb treatment.

journal_name

Immunol Res

journal_title

Immunologic research

authors

Rogers LM,Veeramani S,Weiner GJ

doi

10.1007/s12026-014-8542-z

subject

Has Abstract

pub_date

2014-08-01 00:00:00

pages

203-10

issue

1-3

eissn

0257-277X

issn

1559-0755

journal_volume

59

pub_type

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