Antitumor immunization with a minimal peptide epitope (G9-209-2M) leads to a functionally heterogeneous CTL response

The goal of experimental clinical protocols using peptide antigen for active vaccination and treatment of patients with metastatic cancer is to induce a vigorous cytotoxic T lymphocyte (CTL) response against the immunizing antigen, and thereby against tumor cells expressing the antigen. However, the magnitude and breadth of human CTL responses induced by peptide immunization, and in particular against antigens expressed by normal tissues as well as tumors, is not well characterized. This issue was examined by characterizing CTL cloids derived from peripheral blood mononuclear cells of three patients who received peptide immunization as treatment for metastatic melanoma. All patients received G9-209-2M peptide, a modified epitope of the gp100 melanoma-associated antigen. The results indicated that the CTL response induced by this peptide antigen was highly heterogeneous both in terms of avidity toward the peptide antigen and recognition of tumor cell lines. Furthermore, avidity of each CTL cloid for the native peptide was highly predictive of tumor reactivity. These results are discussed in terms of their implications for peptide vaccination and adoptive tumor immunotherapy.