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

Abstract

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.

Revolutionizing cancer immunotherapy: unleashing the potential of bispecific antibodies for targeted treatment

“…Despite significant progress, BsAb development in oncology remains unfinished. While several BsAbs have gained marketing approval, the rapid emergence of trispecific and multispecific antibodies highlights their dynamic potential (298)(299)(300)(301). Robust validation through larger phase II-III clinical trials across cancer types and individualized treatment regimens will be key to fully harnessing the advantages of BsAbs.…”

Agonism of 4-1BB for immune therapy: a perspective on possibilities and complications

“…A variant example of selective agonism is the creation of CD3 T cell engagers (TCEs) that incorporate antibody binding regions of 4-1BB with CD3, and checkpoint blockade (PD-L1), and a tumor target such as CD19 or EGFR ( Figure 2 ), with the aim of only engaging 4-1BB on a T cell in the TME ( 53 , 107 ). While TCEs are an interesting concept, published work on any incorporating 4-1BB binding is limited, and such a multivalent modality has many potential drawbacks and still risks having off-tumor and off-target effects.…”