Additional strategies to activate effective immunity against poorly immunogenic tumor antigens employ the "DNA fusion genes vaccines" to activate T cell help for antitumor responses. The CD4 + Th cell, as pivotal cell of the immune response able to induce high levels of immunity and the maintenance of the response, has been extensively studied by Stevenson and coworkers [97] . The requirement for foreign sequences to induce Th for the B-cell response and to help the CTL response has been known for many years [98, 99] . Since Th cells control responses to vaccination, it is quite obvious that self-antigens, which do not contain epitopes likely to be recognized by available Th cells, are incapable of inducing immunity. A strategy to activate Th cells for inducing antitumor immunity is to engage a repertoire against nontolerized antigens. The use of xenogeneic antigen to break tolerance is likely due to the presence of some foreign sequences in the xenogeneic antigen that are able to activate Th cells [100] . Focusing on the antimicrobial repertoire, the principle has been applied to realize the DNA fusion gene vaccines encoding the tumor antigen linked to an antigen derived from tetanus toxin. Fusion of the Fragment C (FrC) of tetanus toxin amplified the immune response against a range of tumor antigens, leading to suppression of tumor growth [87] . Clinical trials by using these approaches to breaking self-tolerance for therapeutic purposes in patients with lymphoma and prostate carcinoma are discussed elsewhere.