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.

Abstract

PURPOSE:

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).

PATIENTS AND 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).

CONCLUSION:

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.

• Authors: Craig L Slingluff Jr, Gina R Petroni, Galina V Yamshchikov, Sarah Hibbitts, William W Grosh, Kimberly A Chianese-Bullock, Eric A Bissonette, Donna L Barnd, Donna H Deacon, James W Patterson, Jayashree Parekh, Patrice Y Neese, Elizabeth M H Woodson, Catherine J Wiernasz, Priscilla Merrill
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 22 Issue 22 Pg. 4474-85 (Nov 15 2004) ISSN: 0732-183X [Print] United States
• PMID: 15542798 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Cancer Vaccines
• HLA Antigens
• Interleukin-2
• Membrane Glycoproteins
• Neoplasm Proteins
• PMEL protein, human
• Vaccines, Subunit
• gp100 Melanoma Antigen
• Tyrosine

Topics

• Adult
• Aged
• Antineoplastic Agents (administration & dosage, pharmacology)
• Cancer Vaccines (administration & dosage, immunology, pharmacology)
• Disease-Free Survival
• Drug Administration Schedule
• Female
• HLA Antigens (immunology)
• Humans
• Interleukin-2 (administration & dosage, pharmacology)
• Male
• Melanoma (drug therapy, immunology)
• Membrane Glycoproteins (immunology)
• Middle Aged
• Neoplasm Proteins (immunology)
• Skin Neoplasms (drug therapy, immunology)
• Treatment Outcome
• Tyrosine (immunology)
• Vaccines, Subunit (administration & dosage, immunology, pharmacology)
• gp100 Melanoma Antigen