Anti-Mesothelin/CD3 bispecific mRNA-LNP

Mesothelin (or MSLN), encoded by the MSLN gene, is a glycosylphosphatidylinositol-linked membrane glycoprotein. This glycoprotein is expressed on the cell surface of mesothelioma and is overexpressed in a variety of human tumors, including mesothelioma, ovarian, pancreatic, lung adenocarcinoma, and cholangiocarcinoma. Mesothelin binds to MUC16, and this interaction may promote tumor engraftment and peritoneal spread through cell adhesion. A 64 amino acid region (residues 296-359) at the N-terminal of cell surface mesothelin has been identified as the functional binding domain (termed IAB) of MUC16. Mesothelin acts as a functional partner of MUC16 in cancer development. Therefore, mesothelin can be used as a tumor marker or as an antigenic target for therapeutic cancer vaccines. A human anti-mesothelin CAR has been constructed consisting of a human mesothelin-specific single-chain antibody variable fragment (P4 scFv) conjugated to a T-cell signaling domain. In human T cells cultured with mesothelin-expressing tumors, P4 CAR expression resulted in proinflammatory cytokine production, degranulation, and efficient cytolytic function and killing of mesothelin-negative cancer cells.
This product is designed as a tool for the delivery and expression of anti-Meso P4 scFv/CD3 mutant Fc mRNA for research. The product leverages the lipid nanoparticle (LNP) technology platform for simple and efficient delivery of anti-Meso P4 scFv/CD3 mutant Fc mRNA to a variety of mammalian cells in vitro and in vivo. The LNPs used are formulated with SM-102, DSPC, cholesterol and DMG-PEG2000 at an optimal molar concentration for a high rate of encapsulation and efficient mRNA delivery. The anti-Meso P4 scFv/CD3 mutant Fc in this product is approximately 70 kD and consists of anti-Meso P4 scFv (single-chain variable fragment), mutant human Fc and CD3ze signaling domains. The full-length amino acid sequence of anti-Meso P4 scFv/CD3 mutant Fc mRNA-LNP product is available upon request.