Abstract: The present application is related to a method of treating a cancer by administering to a human subject multiple doses of a mRNA cancer vaccine formulated as a lipid nanoparticle wherein the cancer vaccine comprises one or more mRNAs each having one or more open reading frames encoding 3-50 peptide epitopes, and wherein each of the peptide epitopes are portions of personalized cancer antigens or portions of cancer hotspot antigens. The present application further relates to a method of treating cancer by combining anti-cancer immunotherapy with the administration of the aforementioned mRNA cancer vaccine.

Abstract: The disclosure relates to optimized cancer vaccines, as well as methods of making the vaccines, using the vaccines, and compositions comprising the vaccines. The cancer vaccines comprise personalized cancer antigens or portions of cancer hotspot antigens. Additionally, the disclosure relates to a computerized system for selecting nucleic acids to include in an optimized cancer vaccine.