It is disclosed herein that SPANX-B is uniquely expressed in a number of human tumors and that SPANX-B is an immunogenic antigen that is recognized by human T cells inducing helper CD4+ and cytolytic CD8+ T cell responses. Specific SPANX-B polypeptides and polynucleotides are disclosed that can be used to generate an immune response. In several embodiments, these polypeptides can be used for the treatment of a variety of cancers, including melanoma, colon carcinoma, ovarian cancer, breast cancer, myeloma, lung carcinoma and renal cancer.
