Custom mRNA-4157 Biosimilar Neoantigen Vaccine Development

An mRNA neoantigen vaccine is a personalized cancer immunotherapy utilizing in vitro transcribed mRNAs that encode unique genetic mutations (neoantigens) found in a cancer patient. When injected into this specific patient, the mRNA vaccine instructs T-cells to recognize and attack the cancer cells. For example, intismeran autogene (also known as mRNA-4157 or V940) is an mRNA cancer vaccine that encode 34 unique neoantigens to treat melanoma. BiCell Scientific Inc utilizes the mRNA-4157 scaffold to design its mRNA vaccine. The mRNA-4157 scaffold includes the non-variable backbone consisting in the 34-epitope concatemer, 5′ cap, 5′-UTR, junction linkers, 3′-UTR, and poly(A) tail. The neoantigen epitopes range between 15-30 aa in length. They are mapped from individual patients. The junction linker can be a single glycine, or Gly-Gly in the newest family. Each junction linker is cleaved by proteasome so each epitope’s C-terminus is generated correctly for TAP transport and HLA loading. The 5′-UTR contains a “V1-UTR” core plus a GC-rich CCCCGGCGCC element immediately before the Kozak sequence. The 3′-UTR is a 110nt long sequence derived from the human α-globingene (HBA1).