Impact of cytokine administration on the generation of antitumor reactivity in patients with metastatic melanoma receiving a peptide vaccine

Patients with metastatic melanoma were immunized with an immunodominant pep tide derived from the gp100 melanoma-melanocyte differentiation Ag that was modified to increase binding to HLA-A(+)0201, A total of 10 of 11 patients who received the g209-2M peptide alone developed precursors reactive with the native g209 peptide, compared with only 5 of 16 patients who received g 209-2M peptide plus IL-2 (p(2) = 0.005), Peptide reactivity closely correla ted with the recognition of HLA-A(+)0201 melanoma cells (p < 0.001), The de crease in immune reactivity when peptide was administered with IL-2 appeare d specific for the immunizing peptide, since reactivity to an influenza pep tide resulting from prior exposure was not affected. Preexisting antitumor precursors did not decrease when peptide plus IL-2 was administered. The ad ministration of GM-CSF or IL-12 also resulted in a decrease in circulating precursors compared with the administration of peptide alone, though not as great a decrease as that seen with IL-2, Immunization with peptide plus IL -2 did, however, appear to have clinical impact since 6 of the 16 patients (38%) that received peptide plus IL-2 had objective cancer regressions. It thus appeared possible that immunization with peptide plus IL-2 resulted in sequestering or apoptotic destruction of newly activated immune cells at t he tumor site. These represent the first detailed studies of the impact of immunization,vith tumor peptides in conjunction with a variety of cytokines in patients with metastatic cancer.