Gan, Samuel Ken-En, Derrick, Jeremy P., and Fraternali, Franca (2022) Editorial: Understanding and Engineering Antibody-Superantigen Interactions. Frontiers in Immunology, 13. 857339.

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Abstract

[Extract] Superantigens are classically defined as antigens that induce hyperactivation of the immune system. They are traditionally associated with non-specific activation of T-cells that induces abnormal cytokine release. A search for the term ‘superantigens’ on Google in January 2022 yielded results with a heavy bias towards T-cell superantigens (1–4) which were first described in 1989 (5). Almost 30 years later, the T-cell centric view of superantigens continues to overshadow B-cell or antibody superantigens, even though reports of B-cell superantigens date back at least to 1966 for Protein A (6) and 1984 for Protein G (7). Implementation for antibody purification followed rapidly, assisting the development of therapeutic antibodies. In the early 1990s, applications of superantigens expanded towards potential therapeutics, particularly against cancer (8–11). These earlier studies are now bearing fruition: for example, a recent review of the literature on the application of Staphylococcal enterotoxins in cancer immunotherapy found over 50 studies, of which Staphylococcal enterotoxin A was the most common superantigen employed (12). Fusions of superantigens with, for example, antibody Fab fragments which are targeted against tumour-associated antigens have been shown to be effective against melanoma and other cancers (12). Superantigens have also found recent application in CAR-T therapy; von Scheidt et al. demonstrated that inhibition of solid tumour growth in mice was potentiated by pre-incubation of CAR T cells with Staphylococcal enterotoxin B (13). Although most of these studies to date have used mouse models, translation of some applications to the clinic in the near future seems likely.

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