Tunable Multivalent Platform for Immune Recruitment to Lower Antigen Expressing Cancers

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.

Automated summary

Chemical immunotherapeutic strategies called Antibody Recruiting Molecules (ARMS) have been developed to direct the immune system to clear diseased cells. However, their function is limited against tumors that express lower levels of antigens. To address this limitation, a tunable multivalent immune recruitment (MIR) platform has been developed to amplify and stabilize antibody recruitment to cells with lower antigen levels. This platform, called polymeric ARMS (pARMS), has shown enhanced anti-cancer immune function compared to traditional ARMS in targeting lower antigen expressing cancer cells.