J Immunol 1999 Aug 1;163(3):1690-5
Impact of cytokine administration on the generation of antitumor
reactivity in patients with metastatic melanoma receiving a peptide
vaccine.
Rosenberg SA, Yang JC, Schwartzentruber DJ, Hwu P, Marincola FM, Topalian SL, Restifo NP, Sznol M, Schwarz
SL, Spiess PJ, Wunderlich JR, Seipp CA, Einhorn JH, Rogers-Freezer L, White DE
Surgery Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892,
USA. SAR@nih.gov
Patients with metastatic melanoma were immunized with an immunodominant peptide 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 g209-2M peptide plus IL-2 (p2 = 0.005). Peptide reactivity closely correlated with the
recognition of HLA-A+0201 melanoma cells (p < 0. 001). The decrease in immune reactivity when peptide was administered
with IL-2 appeared specific for the immunizing peptide, since reactivity to an influenza peptide resulting from prior exposure
was not affected. Preexisting antitumor precursors did not decrease when peptide plus IL-2 was administered. The
administration 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 the tumor site. These represent the first detailed studies of the impact of immunization with
tumor peptides in conjunction with a variety of cytokines in patients with metastatic cancer. |
