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Role of antibody-dependent cell-mediated cytotoxicity in the efficacy of therapeutic anti-cancer monoclonal antibodies

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Summary

In recent years, interest in anti-cancer therapeutic monoclonal antibodies (mAb) has been renewed. Several of these reagents have been approved for therapy in a variety of cancer patients and many others are in different stages of development. It is believed that multiple mechanisms are involved in the anti-cancer effects of these reagents. However, several in vitro and in vivo studies have demonstrated that antibody-dependent cell-mediated cytotoxicity (ADCC) is their predominant mode of action against cancer cells. The requirement for a direct interaction between mAb and receptors for the Fc region of the antibodies (FcR) has been demonstrated for anti-tumor effects of these antibodies. Consequently, FcR-bearing immune effector cells play an important role in mediating their effects. It is not surprising that cancer cells have developed different strategies to evade these antibodies. Several strategies are proposed to potentiate the mAb-mediated ADCC in cancer patients. They may enhance anti-cancer therapeutic effects of these regents.

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Abbreviations

ADCC:

Antibody-dependent cell-mediated cytotoxicity

BCR:

B cell receptor complex

CDC:

Complement-dependent cytotoxicity

CDR:

Complementarity determining region

CR-1:

Type 1 complement receptor

DC:

Dendritic cells

Fc:

Fragment crystallisable

FcR:

Receptor for Fc

FDA:

Federal Drug Agency (USA)

G-CSF:

Granulocyte-colony stimulating factor

GM-CSF:

Granulocyte macrophage-colony stimulating factor

IC:

Immune complex

Ig:

Immunoglobulins

ILT-2:

Immunoglobuin like transcript-2

ITAM:

Immunoreceptor tyrosinebased activating motif

ITIM:

Immunoreceptor tyrosine-based inhibitory motif

HIV:

Human Immunodeficiency virus

mAb:

Monoclonal antibody

IFN:

Interferon

KIR:

Killer-cell immunoglobulin-like receptor

KO:

Knockedout

NK cell:

Natural killer cell

RBC:

Red blood cells

SLE:

Systemic Lupus Erythrematosis

TCR:

T cell receptor complex

VEGF:

Vascular endothelial growth factor

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  1. Department of Microbiology & Immunology, Ste-Justine Hospital Research Center, University of Montreal, Quebec, Canada

    Alexandre Iannello & Ali Ahmad

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  1. Alexandre Iannello
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  2. Ali Ahmad
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Correspondence to Ali Ahmad.

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Iannello, A., Ahmad, A. Role of antibody-dependent cell-mediated cytotoxicity in the efficacy of therapeutic anti-cancer monoclonal antibodies. Cancer Metastasis Rev 24, 487–499 (2005). https://doi.org/10.1007/s10555-005-6192-2

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