The Neo-STAT™ Platform – The next generation of Immuno-STATs
The Neo-STAT platform is a variation of the Immuno-STAT™ platform designed with an empty Signal 1 “pocket” enabling easy integration of any tumor-specific protein. Neo-STAT enhances versatility of Cue Biopharma’s biologics to treat a wide range of cancers through “plug-and-play” engineering of bispecific molecules.
Neo-STAT Framework
Signal 1: An unoccupied peptide antigen cleft in the major histocompatibility peptide complex (pMHC), into which different antigens of interest can easily be added to selectively engage disease-relevant T cells of choice
Signal 2, Fc Backbone, and Peptide Linker: Analogous to the core framework of Immuno-STATs
Proof-of-concept studies showed that Immuno-STATs and Neo-STATs carrying the same peptide antigens led to an equivalent potency in stimulating an immune response, and in particular, the activation and expansion of peptide-specific cytotoxic CD8+ T cells.
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Immuno-STAT vs Neo-STAT
The immune response triggered by CUE-100 series Immuno-STAT and Neo-STAT biologics incorporating the immunogenic peptides (1) phosphoprotein 65 (pp65) from cytomegalovirus (CMV) and (2) melanoma associated antigen recognized by T cells-1 (MART-1), expressed by melanoma cells, was compared. Peripheral blood mononuclear cells (PMBCs) derived from subjects exposed to CMV or from melanoma patients, were treated with Immuno-STATs and Neo-STATs incorporating pp65 or MART-1, respectively. The top and middle right panels show that activation and expansion of peptide specific CD8+ T cells occurred to the same extent regardless of whether an Immuno-STAT or Neo-STAT was used, indicating essentially equivalent potency in stimulating an immune response. Activation was also selective such as that PMBCs from donors reactive to CMV Immuno-STAT or Neo-STAT were not reactive to MART-1 Immuno-STAT or Neo-STAT, and vice versa.
In addition, when a Neo-STAT with an immunogenic SARS-CoV-2 peptide was used, it stimulated the proliferation of peptide-specific CD8+ T cells whereas an empty Neo-STAT, with an unoccupied peptide binding cleft, had no effect.
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Key Benefits of the Neo-STAT Platform
- Enables faster and cost-efficient manufacturing
- Increases R&D efficiency by reducing cost of producing clinical grade material
- Enhances platform versatility – Enables targeting of multiple tumor antigens, including post-translationally modified peptides and neo-antigens for personalized therapy
