Research Abstract
Complement Function in mAb-mediated Cancer Immunotherapy
Kyra A. Gelderman1, Stephen Tomlinson2, Gordon D. Ross3 and Arko Gorter1
1Department of Pathology L1-Q, Leiden University Medical Center, Postbox 9600, 2300 RC Leiden, The Netherlands
2Department Microbiology and Immunology, Medical University of South Carolina,
3Tumor Immunology Program, James Graham Brown Cancer Center, University of Louisville
Trends in Immunology Vol.25 No.3 March 2004
Complement activation by mAbs can cause direct
tumor cell lysis or enhance antibody-dependent cell-mediated cytotoxicity. However, tumor cells are protected
from complement-mediated injury by membrane-bound complement regulatory proteins (mCRP) that are often expressed at elevated levels on tumor
cells. Recent studies indicate that blocking or overwhelming the function of tumor cell mCRP might substantially
improve the efficacy of monoclonal antibody
(mAb) immunotherapy. In addition, the use of β-glucan
as an adjuvant for mAb immunotherapy enables iC3b
deposited on tumor cells by mAbs to activate complement
receptor 3 (CR3) on effector cells, thus inducing
CR3-dependent cellular cytotoxicity. These strategies
provide novel cell-mediated mechanisms of tumor
cytotoxicity that are additive to all other mAb effector
mechanisms.