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Review
. 2014 Mar;11(1):20-33.
doi: 10.7497/j.issn.2095-3941.2014.01.002.

Mechanistic considerations for the use of monoclonal antibodies for cancer therapy

Patrick M Glassman  1 , Joseph P Balthasar  1
Affiliations
Review

Mechanistic considerations for the use of monoclonal antibodies for cancer therapy

Patrick M Glassman et al. Cancer Biol Med. 2014 Mar.

Abstract

Since the approval of rituximab in 1997, monoclonal antibodies (mAbs) have become an increasingly important component of therapeutic regimens in oncology. The success of mAbs as a therapeutic class is a result of great strides that have been made in molecular biology and in biotechnology over the past several decades. Currently, there are 14 approved mAb products for oncology indications, and there are ten additional mAbs in late stages of clinical trials. Compared to traditional chemotherapeutic agents, mAbs have several advantages, including a long circulating half-life and high target specificity. Antibodies can serve as cytotoxic agents when administered alone, exerting a pharmacologic effect through several mechanisms involving the antigen binding (Fab) and/or Fc domains of the molecule, and mAbs may also be utilized as drug carriers, targeting a toxic payload to cancer cells. The extremely high affinity of mAbs for their targets, which is desirable with respect to pharmacodynamics (i.e., contributing to the high therapeutic selectivity of mAb), often leads to complex, non-linear, target-mediated pharmacokinetics. In this report, we summarize the pharmacokinetic and pharmacodynamics of mAbs that have been approved and of mAbs that are near approval for oncology indications, with particular focus on the molecular and cellular mechanisms responsible for their disposition and efficacy.

Keywords: Antibodies; monoclonal; oncology; pharmacodynamics; pharmacokinetics.

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Conflict of interest statement

No conflicts of interest are disclosed.

Figures

Figure 1
Figure 1
Pharmacologic Mechanisms of Action for mAbs. Panel A, Inhibition of Cell Signaling via Binding to Soluble Targe; Panel B, Inhibition of Cell Signaling via Binding to Membrane-Bound Receptor; Panel C, Direct Induction of Apoptosis; Panel D, Antibody-Dependent Cellular Cytotoxicity; Panel E, Complement-Dependent Cytotoxicity; Panel F, CD28 Superagonist; Panel G, Delivery of Toxic Payload (Antibody-Drug Conjugate, Immunotoxin, Radioimmunoconjugate).
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