Week 4, Feb 2024: Antibodies for Toxins

Toxins are substances produced by living organisms, such as bacteria, fungi, plants, and animals, that are harmful to other organisms. Antibodies play a crucial role in immune responses for the body's defense against toxin intoxication, in addition to being invaluable tools for both diagnostic and therapeutic applications.

Just this week, researchers used a synthetic human antibody library to find and optimize a monoclonal antibody (mAb) for deadly snakebite toxins that neutralizes long-chain three-finger α-neurotoxins produced by the Elapidae family of snakes (e.g. cobras, kraits, and mambas). The antibody (95Mat5) conferred protection against envenoming in mice and functioned by mimicking the binding between the toxins and their receptors. Snakebite envenoming is a major global public health concern, causing approximately 81,000 to 138,000 deaths each year. Improved therapies are urgently needed, but development is challenging due to the antigenic diversity in snake venom toxins from different species.

Broadly-neutralizing mAbs (bnAbs) targeting animal toxins have also been developed using various methods such as cross-panning strategies in phage display selection campaigns, semi-rational design and directed evolution, and by high-throughput screening of B-cells from immunized individuals. This month, a study demonstrated the successful discovery of bnAbs against brown recluse spider and Gadim scorpion sphingomyelinases using consensus toxins as antigens.

Currently, efficient detection and quantification of toxins in complex matrices including environmental, food, and clinical matrices are needed, and combining antibodies with methods like mass spectrometry (MS) can help with that. MS offers high sensitivity, selectivity, and capability to handle complex mixtures, making it an ideal analytical technique for the identification and quantification of food toxins. A recent review describes various advances in this area, including the IAC-MS technique involving immunoaffinity chromatography and antibody-based columns.

Reversely, toxins themselves can be combined with antibodies as a therapeutic drug, with a recent paper by Rodak et al. reporting the development of a cytotoxic antibody-drug conjugate (ADC) targeting membrane IgE-positive cells. Due to the fast internalization and strict target specificity, this ADC presents a starting point for therapies of allergic conditions, atopic dermatitis, and IgE myeloma.