An Fc Binding Peptide-Based Facile and Versatile Build Platform for Multispecific Antibodies

Multispecific antibodies (MsAbs) maintain the specificity of versatile antibodies while simultaneously addressing different epitopes for a cumulative, collaborative effect. They could be an alternative treatment to chimeric antigen receptor-T cell therapy by helping to redirect T cells to tumors in vivo. However, one major limitation of their development is their relatively complex production process, which involves performance of a massive screen with low yield, inconsistent quality, and nonnegligible impurities. Here, a poly(l-glutamic acid)-conjugated multiple Fc binding peptide-based synthesis nanoplatform was proposed, in which MsAbs were constructed by mixing the desired monoclonal antibodies (mAbs) with polymeric Fc binding peptides in aqueous solution without purification. To determine its efficacy, a dual immune checkpoint-based PD1/OX40 bispecific antibody and PDL1/CD3e/4-1BB trispecific antibody-based T cell engager were generated to trigger antitumor CD8⁺ T responses in mice, showing superior tumor suppression over free mixed mAbs. In this study, a facile, versatile build platform for MsAbs was established.