Methods for preparing ex vivo T cell cultures using IL-21 compositions for use in adoptive immunotherapy are described. Addition of IL-21 to cultures of non-terminally differentiated T cells population, either isolated or present in peripheral blood mononuclear cells are exposed to one or more tumor antigens, and in the presence of IL-21 compositions and antigen presenting cells (APCs), the resulting T cell population has an enhanced antigen-specificity, and can be reintroduced into the patient. Methods are also disclosed for identifying tumor antigens by culturing T cell populations exposed to IL-21 compositions and APCs in the presence of tumor material.