Adaptabodies: Retargeting a Predefined Monoclonal Antibody With Bispecific Nanobodies for Antibody Therapy

Abstract

Monoclonal antibody (MoAb) therapy is a cornerstone in treating cancer, inflammatory diseases, and infections. However, the development of new monoclonal antibodies is labor-intensive, costly, and species-specific, limiting their accessibility in veterinary medicine and slowing innovation in human therapies. In this work, we introduce adaptabodies, bispecific nanobody constructs that repurpose existing MoAbs, of irrelevant specificity, by bridging their idiotype to a new antigen. As a proof of concept, we tested this strategy using a model murine MoAb combined with a neutralizing adaptabody that redirected its binding to tetanus toxin and resulted in mice surviving at least for 8 days when challenged with 1 lethal dose 100 (LD₁₀₀). Mice challenged with 20 LD₁₀₀ of tetanus toxin and treated with two neutralizing adaptabodies survived 8 days and increasing five-fold the amount of the MoAb increased survival to at least 20 days. This approach reduces the need to develop new monoclonal antibodies for each disease, requiring only the retargeting domain to be generated. Moreover, a single MoAb could be developed for species lacking therapeutic MoAbs for adaptabody-mediated treatment. The increasing approval of monoclonal antibodies for treatment of both humans and companion animals underscores the relevance of this flexible and scalable strategy.