Human Monoclonal Antibodies as a New Class of Antiinfective Compounds

Roberto Burioni,Alois B. Lang,J. Donald Capra

doi:10.1155/2013/297120

Roberto Burioni, Alois B. Lang + Show 1 more

Open Access

https://doi.org/10.1155/2013/297120

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Abstract

The concept of using “magic bullets” in the fight against infectious diseases was originally proposed by Paul Ehrlich, one of the founding fathers of immunology and of the basis of antiinfective therapy [1]. These “magic” compounds should have been able to target microbes without harming the infected host. Actually, this concept is the mainstay of antiinfective therapy, as we still know it today. What Dr. Ehrlich did not and could not foresee was the microbial ability of using “magic tricks” against therapeutic compounds, that is, of developing resistance mechanisms. This is true for all groups of pathogens and all classes of antiinfective drugs, making the need of reliable alternatives everyday more compelling [2–5].

Highlights

Since their first description in 1975 [6], monoclonal antibodies have been depicted as ideal “magic bullets” due to their extremely specific mode of action, associated with an extreme biotechnological versatility [7]
A monoclonal antibodies (mAbs) with potential therapeutic utility should fulfill at least the following three conditions: (i) specific binding to the molecular target by the antigen-binding fragment (Fab) domain, (ii) effective, but controlled, effector functions activated by binding of the constant crystallizable fragment (Fc) region to specific receptors of immune cells, and (iii) good pharmacokinetic characteristics
The first mAbs were exclusively of animal origin, with dramatic potential drawbacks in terms of high immunogenicity, short half-life, and low capacity of activating Fc-mediated effector functions when administered to patients

Summary

Introduction

Since their first description in 1975 [6], monoclonal antibodies (mAbs) have been depicted as ideal “magic bullets” due to their extremely specific mode of action, associated with an extreme biotechnological versatility [7]. A mAb with potential therapeutic utility should fulfill at least the following three conditions: (i) specific binding to the molecular target by the antigen-binding fragment (Fab) domain, (ii) effective, but controlled, effector functions activated by binding of the constant crystallizable fragment (Fc) region to specific receptors of immune cells, and (iii) good pharmacokinetic characteristics. The first mAbs were exclusively of animal (murine) origin, with dramatic potential drawbacks in terms of high immunogenicity, short half-life, and low capacity of activating Fc-mediated effector functions when administered to patients.

Results

Conclusion