Tumor-reactive T helper lymphocytes recognize a promiscuous MAGE-A3 epitope presented by various major histocompatibility complex class II alleles

The development of effective T cell-based immunotherapy for cancer requires the identification of antigens capable of inducing both CTL, and T helper immune responses. Although CTLs will participate in the antitumor response mainly by exerting their lytic activity on the tumor cells, helper T lympho cytes wilt be critical for the induction and maintenance of the CTLs, Thus, effective subunit therapeutic vaccines should include both CTL and T helpe r epitopes from antigens expressed on the tumor cells, The product of the M AGE-A3 gene is an attractive candidate for tumor immunotherapy because it i s expressed in the majority of melanomas and in a great proportion of other solid tumors. Although numerous CTL epitopes for the MAGE-A3 antigen have been reported, only a few have been described for helper T cells. Here we s how that a synthetic peptide derived from the MAGE-A3 sequence (MAGE-A3(146 -160)) was effective in inducing in vitro T helper responses in the context of HLA-DR1 and HLA-DR7 alleles, Most significantly, the peptide-reactive h elper T lymphocytes were capable of recognizing various forms of MAGE-A3 an tigen (tumor cell lysates, dead/apoptotic tumor cells, or recombinant MAGE- A3 protein), indicating that the T-cell epitope represented by peptide MAGE -A3(146-160) is naturally processed by antigen-presenting cells. These stud ies are relevant for the design of multi-epitope vaccines for treating MAGE -A3-expressing tumors through the simultaneous stimulation of CTL and T hel per lymphocytes.