Tunable Multivalent Platform for Immune Recruitment to Lower Antigen Expressing Cancers
Language English Country Germany Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- Keywords
- Antibodies, Cell Recognition, Drug Design, Immunochemistry, Polymers,
- MeSH
- Antigens * MeSH
- Phagocytosis MeSH
- Humans MeSH
- Prostatic Neoplasms * MeSH
- Antibodies chemistry MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antigens * MeSH
- Antibodies MeSH
Chemical immunotherapeutic strategies including Antibody Recruiting Molecules (ARMs - bivalent small molecules containing an antibody-binding domain (ABD) and a target-binding domain (TBD)) direct immune-mediated clearance of diseased cells. Anti-cancer ARM function relies on high tumor antigen valency, limiting function against lower antigen expressing tumors. To address this limitation, we report a tunable multivalent immune recruitment (MIR) platform to amplify/stabilize antibody recruitment to cells with lower antigen valencies. An initial set of polymeric ARMs (pARMs) were synthesized and screened to evaluate ABD/TBD copy number, ratio, and steric occlusion on specific immune induction. Most pARMs demonstrated simultaneous high avidity binding to anti-dinitrophenyl antibodies and prostate-specific membrane antigens on prostate cancer. Optimized pARMs mediated enhanced anti-cancer immune function against lower antigen expressing target cells compared to an analogous ARM.
Department of Chemistry and Chemical Biology McMaster University Hamilton Ontario L8S 4L8 Canada
School of Biomedical Engineering McMaster University Hamilton Ontario L8S 4M1 Canada
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