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Toxins 2015, 7(6), 1854-1881;

Monoclonal Antibody Combinations that Present Synergistic Neutralizing Activity: A Platform for Next-Generation Anti-Toxin Drugs

Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona 7410001, Israel
Author to whom correspondence should be addressed.
Academic Editor: Azzam A. Maghazachi
Received: 5 March 2015 / Revised: 7 May 2015 / Accepted: 19 May 2015 / Published: 29 May 2015
(This article belongs to the Collection Toxicity and Therapeutic Interventions in the Immune System)
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Monoclonal antibodies (MAbs) are among the fastest-growing therapeutics and are being developed for a broad range of indications, including the neutralization of toxins, bacteria and viruses. Nevertheless, MAbs potency is still relatively low when compared to conventional polyclonal Ab preparations. Moreover, the efficacy of an individual neutralizing MAb may significantly be hampered by the potential absence or modification of its target epitope in a mutant or subtype of the infectious agent. These limitations of individual neutralizing MAbs can be overcome by using oligoclonal combinations of several MAbs with different specificities to the target antigen. Studies conducted in our lab and by others show that such combined MAb preparation may present substantial synergy in its potency over the calculated additive potency of its individual MAb components. Moreover, oligoclonal preparation is expected to be better suited to compensating for reduced efficacy due to epitope variation. In this review, the synergistic neutralization properties of combined oligoclonal Ab preparations are described. The effect of Ab affinity, autologous Fc fraction, and targeting a critical number of epitopes, as well as the unexpected contribution of non-neutralizing clones to the synergistic neutralizing effect are presented and discussed. View Full-Text
Keywords: MAbs; oligoclonal; combination; neutralization; synergism; toxin MAbs; oligoclonal; combination; neutralization; synergism; toxin

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Diamant, E.; Torgeman, A.; Ozeri, E.; Zichel, R. Monoclonal Antibody Combinations that Present Synergistic Neutralizing Activity: A Platform for Next-Generation Anti-Toxin Drugs. Toxins 2015, 7, 1854-1881.

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