Targeting Solid Cancers with Dual-Action Antibodies: Mesothelin and CD47 Co-Blocking Strategy

The abstract discusses a novel approach to cancer treatment using bispecific antibodies (biAbs) targeting mesothelin (MSLN) and CD47. MSLN is a protein with low expression in healthy tissues but is highly present in various solid tumors, including mesothelioma and cancers of the pancreas, bile ducts, ovaries, lungs, and stomach. CD47 is another protein that is upregulated in many cancers and plays a role in immune evasion by inhibiting phagocytosis of tumor cells. The study presents a series of biAbs that selectively bind to MSLN-positive cancer cells without affecting healthy cells that express CD47 at physiological levels. These biAbs are designed to block the interaction between CD47 and its receptor, signal-regulatory protein alpha (SIRPα), in a tumor-specific manner, potentially avoiding issues related to the widespread expression of CD47 in the body.

In vitro testing of these biAbs against different MSLN epitopes showed enhanced cancer cell killing through antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC) mechanisms, outperforming standard monoclonal antibodies (mAbs) and a therapeutic anti-MSLN mAb currently in clinical trials. The biAbs also demonstrated superior efficacy in controlling tumor growth in mouse xenograft models. The findings suggest that MSLN/CD47 biAbs could offer a safe and effective strategy for targeting CD47 in solid tumors, supporting the idea of tumor-directed blockade of CD47 as a new therapeutic approach in cancer treatment.

The research was presented at the American Association for Cancer Research Annual Meeting in 2018, with the authors including Valéry Moine, Lucile Broyer, Xavier Chauchet, and others, as listed in the citation.