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

Area of Science:

• Biotechnology
• Immunology
• Nanotechnology

Background:

• Multispecific antibodies (MsAbs) offer therapeutic potential by targeting multiple epitopes simultaneously, potentially serving as an alternative to chimeric antigen receptor-T cell therapy for redirecting T cells to tumors.
• Current MsAb development faces limitations due to complex production processes, including low yields, inconsistent quality, and impurities from extensive screening.

Purpose of the Study:

• To establish a facile and versatile synthesis platform for constructing multispecific antibodies (MsAbs).
• To demonstrate the efficacy of MsAbs produced via this platform in triggering antitumor responses.

Main Methods:

• A novel poly(l-glutamic acid)-conjugated multiple Fc binding peptide-based nanoplatform was utilized for MsAb synthesis.
• Monoclonal antibodies (mAbs) were mixed with polymeric Fc binding peptides in aqueous solution without purification to construct MsAbs.
• Dual immune checkpoint-based PD1/OX40 bispecific antibodies and PDL1/CD3e/4-1BB trispecific antibody-based T cell engagers were generated.

Main Results:

• The proposed nanoplatform enabled the construction of MsAbs through a simplified, purification-free process.
• Generated bispecific and trispecific antibodies effectively triggered antitumor CD8+ T cell responses in mice.
• MsAbs produced via the platform demonstrated superior tumor suppression compared to free mixed mAbs.

Conclusions:

• A facile and versatile build platform for multispecific antibodies (MsAbs) has been successfully established.
• This platform overcomes the limitations of traditional MsAb production, offering improved yield and quality.
• The developed MsAbs show significant potential for enhancing T cell-mediated antitumor immunity.