Caroline Farmer, MS
Albert Einstein College of Medicine
Bio-Orthogonal Coupling Strategies for a Universal, Personalized, On-Demand Biologics Platform for Endogenous T Cell Therapy
We have developed a precision biologics platform, Immuno-STAT (IST), that recapitulates key antigen-specific and costimulatory signals of the immunological synapse and is being evaluated in clinical trials for multiple oncology indications. Each IST incorporates an MHC molecule covalently linked to an antigenic peptide and costimulatory modules (MODs), enabling selective activation of disease-relevant T cells while sparing the remainder of the T cell repertoire and minimizing the off-target effects associated with global immunotherapies. The platform is highly modular, as replacing the peptide enables targeting of new disease indications, while substituting the MOD enables exploration of new mechanisms. We aim to rapidly produce personalized IST cocktails that leverage each patient’s unique neoantigen repertoire. Currently, each new peptide-MHC combination requires renewed CMC and cGMP efforts, and recombinant production can take 12 months. To overcome this barrier, we are developing empty ISTs that retain structural integrity without peptide and serve as off-the-shelf, universal scaffolds for rapid, site-specific coupling of synthetic peptides, including post-translationally modified neoantigens. This strategy decouples IST production from full recombinant manufacturing and shifts the rate-limiting step to peptide synthesis, which can be completed within a clinically relevant time frame.
We have developed a precision biologics platform, Immuno-STAT (IST), that recapitulates key antigen-specific and costimulatory signals of the immunological synapse and is being evaluated in clinical trials for multiple oncology indications. Each IST incorporates an MHC molecule covalently linked to an antigenic peptide and costimulatory modules (MODs), enabling selective activation of disease-relevant T cells while sparing the remainder of the T cell repertoire and minimizing the off-target effects associated with global immunotherapies. The platform is highly modular, as replacing the peptide enables targeting of new disease indications, while substituting the MOD enables exploration of new mechanisms. We aim to rapidly produce personalized IST cocktails that leverage each patient’s unique neoantigen repertoire. Currently, each new peptide-MHC combination requires renewed CMC and cGMP efforts, and recombinant production can take 12 months. To overcome this barrier, we are developing empty ISTs that retain structural integrity without peptide and serve as off-the-shelf, universal scaffolds for rapid, site-specific coupling of synthetic peptides, including post-translationally modified neoantigens. This strategy decouples IST production from full recombinant manufacturing and shifts the rate-limiting step to peptide synthesis, which can be completed within a clinically relevant time frame.
