Pros and cons of different therapeutic antibody formats for recombinant antivenom development

Abstract

Antibody technologies are being increasingly applied in the field of toxinology. Fuelled by the many advances in immunology, synthetic biology, and antibody research, different approaches and antibody formats are being investigated for the ability to neutralize animal toxins. These different molecular formats each have their own therapeutic characteristics. In this review, we provide an overview of the advances made in the development of toxin-targeting antibodies, and discuss the benefits and drawbacks of different antibody formats in relation to their ability to neutralize toxins, pharmacokinetic features, propensity to cause adverse reactions, formulation, and expression for research and development (R&D) purposes and large-scale manufacturing. A research trend seems to be emerging towards the use of human antibody formats as well as camelid heavy-domain antibody fragments due to their compatibility with the human immune system, beneficial therapeutic properties, and the ability to manufacture these molecules cost-effectively.

Pathogenesis of local necrosis induced by Naja atra venom: Assessment of the neutralization ability of Taiwanese freeze-dried neurotoxic antivenom in animal models

“…Given our finding that FNAV is, at best, only partially effective in controlling the local necrotic damage induced by N. atra venom, it is important to develop novel therapeutic interventions for treating N. atra envenomation in Taiwan. Several advanced biotechnological tools have recently been adopted for developing alternative strategies for antivenom production [53,54]. Applying expertise in synthetic biology, antibody research and immunology, a number of researchers have attempted to develop recombinant antivenoms and investigate their ability to neutralize toxins from snake venom [55][56][57][58][59].…”

Recent Advances in Next Generation Snakebite Antivenoms

“…The authors achieved a yield of 0.2 g antibodies per kg of plant leaves [43], which is indeed impressive, as limited efforts had been applied to optimising expression. However, this does not compare favourably with standardised mammalian cell cultivation approaches, that routinely achieve yields of 5 g/L of correctly folded and secreted IgGs [19], with exceptional examples even reaching 27 g/L [44]. Julve Parreño et al also argue that production of oligoclonal antibody mixtures by parallel batch expression is not economically feasible without compromising efficacy, as many antibodies are needed to target the large arsenal of toxins present in snake venoms [43].…”

“…Antivenoms were first envisioned in their current form by A. Calmette and C. Phisalix in 1894 [15]. Despite recent reports on innovative approaches for developing a new generation of antivenoms based on biotechnological methods, medicinal chemistry, and antibody technologies [16][17][18], plasmaderived antivenoms of animal origin remain the only effective treatment against snakebite envenoming [19,20]. Due to its severity, the World Health Organisation (WHO) recently reinstated snakebite envenoming on its list of Neglected Tropical Diseases [21] and set down a working group that will develop an official strategy for prevention and treatment of snakebite envenoming (http://www.who.int/snakebites/control/WHO_Working_Group_on_Snakebite_Envenoming/en/).…”

Loxoscelism: Advances and Challenges in the Design of Antibody Fragments with Therapeutic Potential

“…This observation is in agreement with previous overlapping peptide scanning analysis, and also screening of peptide phage-display libraries which identified a putative epitope region located far from the catalytic and Mg 2+ -binding sites of the enzyme [28,29,56]. This is not entirely surprising given that, unlike small neurotoxins which are usually recognized by antibodies at their pharmacological site, larger enzymatic toxins such as PLD are neutralized via other effects such as steric hindrance, making this the first ever reported antibody to neutralize animal toxins via this mechanism [57][58][59]. With its typical minimal size, the monovalent scFv 15 hLi7 could not meet this requirement.…”