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.