Immunologic and clinical outcomes of vaccination with a multiepitope melanoma peptide vaccine plus low-dose interleukin-2 administered either concurrently or on a delayed schedule.
OBJECTIVE
A phase II trial was performed to test whether systemic low-dose interleukin-2 (IL-2) augments T-cell immune responses to a multipeptide melanoma vaccine. Forty patients with resected stage IIB-IV melanoma were randomly assigned to vaccination with four gp100- and tyrosinase-derived peptides restricted by human leukocyte antigen (HLA) -A1, HLA-A2, and HLA-A3, and a tetanus helper peptide plus IL-2 administered daily either beginning day 7 (group 1), or beginning day 28 (group 2).


METHODS
T-cell responses were assessed by an interferon gamma ELIspot assay in peripheral blood lymphocytes (PBL) and in a lymph node draining a vaccination site (sentinel immunized node [SIN]). Patients were followed for disease-free and overall survival.


RESULTS
T-cell responses to the melanoma peptides were observed in 37% of PBL and 38% of SINs in group 1, and in 53% of PBL and 83% of SINs in group 2. The magnitude of T-cell response was higher in group 2. The tyrosinase peptides DAEKSDICTDEY and YMDGTMSQV were more immunogenic than the gp100 peptides YLEPGPVTA and ALLAVGATK. T-cell responses were detected in the SINs more frequently, and with higher magnitude, than responses in the PBL. Disease-free survival estimates at 2 years were 39% (95% CI, 18% to 61%) for group 1, and 50% (95% CI, 28% to 72%) for group 2 (P = .32).


CONCLUSIONS
The results of this study support the safety and immunogenicity of a vaccine composed of four peptides derived from gp100 and tyrosinase. The low-dose IL-2 regimen used for group 1 paradoxically diminishes the magnitude and frequency of cytotoxic T lymphocyte responses to these peptides.
Slingluff
Craig L
CL
Department of Surgery, Human Immune Therapy Center, University of Virginia Health System, Charlottesville, VA 22908, USA. cls8h@virginia.edu
Petroni
Gina R
GR
Yamshchikov
Galina V
GV
Hibbitts
Sarah
S
Grosh
William W
WW
Chianese-Bullock
Kimberly A
KA
Bissonette
Eric A
EA
Barnd
Donna L
DL
Deacon
Donna H
DH
Patterson
James W
JW
Parekh
Jayashree
J
Neese
Patrice Y
PY
Woodson
Elizabeth M H
EM
Wiernasz
Catherine J
CJ
Merrill
Priscilla
P
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D016896:Treatment Outcome; D014443:Tyrosine / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology*; D058951:gp100 Melanoma Antigen
D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D006680:HLA Antigens; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D022223:Vaccines, Subunit; D058951:gp100 Melanoma Antigen; D014443:Tyrosine