The concept of using a molecule with more than one binding site to enhance its biological function has been around for some time. Polyspecific antibodies are the basis of a new class of anticancer agents which offer the potential to be directed at multiple tumour antigens to eradicate tumour cells more precisely and effectively.
Polyspecific monoclonal antibodies are genetically engineered proteins that can simultaneously engage two or more different types of epitopes. There are many building block formats to generate BsAbs and TsAbs based on combining the antigen recognition domains of monoclonal antibodies (mAbs).
Bispecific antibodies and trispecific antibodies offer a range of advantages over monoclonal antibodies. This includes that they can redirect specific polyclonal immune cells such as T cells and NK cells to tumour cells to enhance tumour killing, or simultaneously block two different pathways with unique or overlapping functions in pathogenesis.
Additionally, BsAbs and TsAbs potentially increase binding specificity by interacting with multiple different cell surface antigens instead of one, as well as reducing development and production costs when compared to multiple single based antibodies used in combination therapy or compared to the production of CAR-T cells.
Preclinical studies and early phase clinical trials have demonstrated that bispecific and trispecific antibody therapy offer improved treatment of solid tumour malignancies and highlights the potential they hold for future therapies to come.
