CV301 + M7824 + N-803 + NHS-IL12

CV301 + M7824 + N-803 + NHS-IL12 is an investigational combination immunotherapy regimen for cancer, particularly advanced microsatellite stable (MSS) or proficient mismatch repair (pMMR) colorectal cancer and small bowel cancers. The combination includes: - **CV301**: A poxviral-based therapeutic cancer vaccine targeting the tumor-associated antigens CEA and MUC1, delivered via a prime/boost strategy using Modified Vaccinia Ankara (MVA) and Fowlpox vectors. It also encodes three co-stimulatory molecules (B7.1, ICAM‑1, LFA‑3; collectively called TRICOM), designed to enhance T-cell activation against tumors[3][4][7][9]. - **M7824**: Also known as bintrafusp alfa or BA, this is a bifunctional fusion protein that simultaneously targets PD-L1 and sequesters TGF-beta in the tumor microenvironment. It acts as both an immune checkpoint inhibitor and a TGF-beta trap[7]. - **N‑803**: An IL‑15 superagonist complex that stimulates proliferation and activation of natural killer (NK) cells and CD8+ T cells to promote anti-tumor immunity[7]. - **NHS‑IL12**: Also known as M9241, this is a tumor-targeted immunocytokine consisting of two IL‑12 heterodimers fused to the human IgG antibody NHS76. It delivers IL‑12 directly to necrotic regions within tumors by binding exposed DNA, thereby enhancing local immune responses while reducing systemic toxicity[6][8]. This quadruple therapy aims to synergistically activate both innate and adaptive immunity through antigen-specific vaccination, checkpoint inhibition/TGF-beta blockade, cytokine-driven lymphocyte expansion/activation, and targeted delivery of pro-inflammatory cytokines.