Engineering Venom’s Toxin-Neutralizing Antibody Fragments and Its Therapeutic Potential

Abstract

Serum therapy remains the only specific treatment against envenoming, but anti-venoms are still prepared by fragmentation of polyclonal antibodies isolated from hyper-immunized horse serum. Most of these anti-venoms are considered to be efficient, but their production is tedious, and their use may be associated with adverse effects. Recombinant antibodies and smaller functional units are now emerging as credible alternatives and constitute a source of still unexploited biomolecules capable of neutralizing venoms. This review will be a walk through the technologies that have recently been applied leading to novel antibody formats with better properties in terms of homogeneity, specific activity and possible safety.

Workgroup Report by the Joint Task Force Involving American Academy of Allergy, Asthma & Immunology (AAAAI); Food Allergy, Anaphylaxis, Dermatology and Drug Allergy (FADDA) (Adverse Reactions to Foods Committee and Adverse Reactions to Drugs, Biologicals, and Latex Committee); and the Centers for Disease Control and Prevention Botulism Clinical Treatment Guidelines Workgroup—Allergic Reactions to Botulinum Antitoxin: A Systematic Review

“…Neutralizing equine botulinum antitoxin is primarily composed of IgG T , a highly glycosylated IgG that is particularly immunogenic in humans [23,24]. Studies of equine antisera to venoms have shown that no more than 20% of equine antibodies in antitoxin are directed specifically against the target toxin, whereas <5% are neutralizing antibodies, some with overlapping neutralizing epitopes with different affinities [25]. This combination leads to a low activity-to-volume ratio, requiring higher doses [25].…”

“…Studies of equine antisera to venoms have shown that no more than 20% of equine antibodies in antitoxin are directed specifically against the target toxin, whereas <5% are neutralizing antibodies, some with overlapping neutralizing epitopes with different affinities [25]. This combination leads to a low activity-to-volume ratio, requiring higher doses [25]. The percentage of neutralizing antibody produced by the same mechanism to botulinum is likely similar.…”

“…Advances include pepsin or papain digestion to extract the F(abʹ) 2 or Fab portion of the antibody, followed by salt or caprylic acid precipitation of allergenic equine carbohydrate moieties. Ion-exchange chromatography may be used to remove traces of contaminants [25]. In theory, these processes decrease the potential for the products to induce an IgE-mediated response, though remnants of these additives may themselves induce reactions in susceptible individuals.…”

In vitro determination of the efficacy of scorpion venoms as anti-cancer agents against colorectal cancer cells: a nano-liposomal delivery approach

“…17 Many of these components have been found with the unique properties to circumvent the global therapeutic challenges. 18 Venoms and purified toxins of scorpion, such as chlorotoxin (a 36-amino acid peptide), are effective inhibitors of glioma cells. A synthetic peptide from chlorotoxin (TM-601) has the capability to cross the blood-brain barrier, and it is also used in clinical trials for treating glioma.…”

Generation of recombinant antibody fragments with toxin-neutralizing potential in loxoscelism

“…In this context, the cost of pharmaceutical development has dramatically decreased making possible to consider the rise of recombinant antibodies for the treatment of orphan and rare diseases [7]. In the mean time, a considered number of early preclinical studies have clearly demonstrated the potential of anti-toxins recombinant antibody fragments for a "targeted" therapy toward the treatment envenomings, with improved efficacy and safety [8][9][10].…”