A method of treating and / or preventing cancer in a subject, preferably mammalian, more preferably human, by administering in an effective amount IL-21 polypeptide, polynucleotide, vector comprising an IL-21 nucleic acid sequence encoding an IL-21 polypeptide, variants, and fragments thereof, thereby acting as an anti-cancer agent by reducing, ameliorating, and / or eliminating the cancer; and a method of treating and / or preventing cancer in a subject by co-administering the IL-21 polypeptide, polynucleotide, IL-21 vector, variant, and fragments thereof, with an immunotherapeutic and / or chemotherapeutic agent for the treatment and / or prevention of cancer in a subject.