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Review
. 2010 May;10(5):317-27.
doi: 10.1038/nri2744.

Monoclonal antibodies: versatile platforms for cancer immunotherapy

Louis M Weiner  1 , Rishi Surana, Shangzi Wang
Affiliations
Review

Monoclonal antibodies: versatile platforms for cancer immunotherapy

Louis M Weiner et al. Nat Rev Immunol. 2010 May.

Abstract

Antibodies are important therapeutic agents for cancer. Recently, it has become clear that antibodies possess several clinically relevant mechanisms of action. Many clinically useful antibodies can manipulate tumour-related signalling. In addition, antibodies exhibit various immunomodulatory properties and, by directly activating or inhibiting molecules of the immune system, antibodies can promote the induction of antitumour immune responses. These immunomodulatory properties can form the basis for new cancer treatment strategies.

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Conflict of interest statement

Competing financial interests

The authors declare no competing financial interests.

Figures

Figure 1
Figure 1
100 years of Progress-From “Magic Bullets” to Clinical Reality.
Figure 2
Figure 2. IgG structure and function
IgG is composed of two heavy and light chains consisting of constant regions, which contribute to the Fc domain, and variable regions, which contribute to antigen specificity (panel A). Antigen coated with IgG can bind Fc receptors and initiate signalling through immunoreceptor tyrosine-based activation motifs (ITAMs) or immunoreceptor tyrosine-based inibitory motifs (ITIMs) (panel B). IgG can bind neonatal Fc receptors (FcRn) on endothelial cells to maintain serum IgG levels (panel C) or bind to tumour cells and recruit C1q to initiate the complement cascade, resulting in tumour cell lysis by the membrane attack complex (MAC) (panel D).
Figure 3
Figure 3. Anti-tumour mechanisms mediated by IgG–FcγR interactions
Antibody-dependent cell cytotoxicity (ADCC) is initiated by the recognition of IgG-coated tumours by FcγRs, which are expressed by effector immune cells such as NK cells, macrophages, and neutrophils. These interactions lead to ADCC and tumour cell apoptosis, which is mediated by the delivery of perforin and granzymes to the tumour cell (panel A). The IgG-coated apoptotic tumour cells can bind Fc receptors on phagocytes and initiate Fc-dependent phagocytosis, leading to the lysosomal degradation of the tumour cell (panel B). Peptides derived from lysosomal degradation of tumour cells can be loaded onto MHC class II molecules, leading to the activation of CD4+ helper T cells. In addition to CD4+ T cell activation, dendritic cells can cross-present tumour cell antigens and prime cytotoxic CD8+ T cells (panel C).
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