MHC-presented Neoantigen and Carcinoembryonic Antigen (pMHC (NeoAg/CEA))

The target refers to a therapeutic complex consisting of tumor-specific neoantigens and tumor-associated antigens (TAAs) presented on Major Histocompatibility Complex (MHC) molecules for recognition by T-cell receptors (TCRs). Specifically, this target profile includes patient-specific neoantigens derived from frameshift mutations—which are highly immunogenic, non-self peptides resulting from genetic indels—and the carcinoembryonic antigen (CEA), a well-characterized oncofetal protein overexpressed in various adenocarcinomas. Frameshift-derived neoantigens are particularly prevalent in microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) tumors, such as those found in Lynch syndrome and certain colorectal cancers. Therapeutic strategies targeting this complex, such as Gritstone Bio's GRANITE and SLATE platforms or Nouscom's Nous-209, utilize viral vectors or self-amplifying mRNA to prime and boost the immune system to generate a robust, multi-epitope T-cell response. By combining highly specific neoantigens with a broadly expressed TAA like CEA, these therapies aim to overcome tumor heterogeneity and prevent immune escape, often in conjunction with immune checkpoint inhibitors to enhance clinical efficacy.

Other names

Neoantigen-MHC complexCEA-MHC complexFrameshift neoantigen-MHC complexTumor-specific and associated antigen complexpMHC (NeoAg/CEA)

Active immunization via viral vector or mRNA delivery to induce T-cell responses against MHC-presented tumor antigens.