Vaccination with Melanoma Helper Peptides Induces Antibody Responses Associated with Improved Overall Survival.

Abstract

PURPOSE:

A melanoma vaccine incorporating six peptides designed to induce helper T-cell responses to melanoma antigens has induced Th1-dominant CD4(+) T-cell responses in most patients, and induced durable clinical responses or stable disease in 24% of evaluable patients. The present study tested whether this vaccine also induced antibody (Ab) responses to each peptide, and whether Ab responses were associated with T-cell responses and with clinical outcome.

EXPERIMENTAL DESIGN:

Serum samples were studied from 35 patients with stage III-IV melanomas vaccinated with 6 melanoma helper peptides (6MHP). IgG Ab responses were measured by ELISA. Associations with immune response and overall survival were assessed by log-rank test and χ(2) analysis of Kaplan-Meier data.

RESULTS:

Ab responses to 6MHP were detected by week 7 in 77% of patients, and increased to peak 6 weeks after the last vaccine and persisted to 6 months. Ab responses were induced most frequently to longer peptides. Of those with T-cell responses, 82% had early Ab responses. Survival was improved for patients with early Ab response (P = 0.0011) or with early T-cell response (P < 0.006), and was best for those with both Ab and T-cell responses (P = 0.0002).

CONCLUSIONS:

Vaccination with helper peptides induced both Ab responses and T-cell responses, associated with favorable clinical outcome. Such immune responses may predict favorable clinical outcome to guide combination immunotherapy. Further studies are warranted to understand mechanisms of interaction of these Abs, T-cell responses, and tumor control.

• Authors: Caroline M Reed, Nicole D Cresce, Ileana S Mauldin, Craig L Slingluff Jr, Walter C Olson
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 21 Issue 17 Pg. 3879-87 (Sep 01 2015) ISSN: 1557-3265 [Electronic] United States
• PMID: 25967144 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2015 American Association for Cancer Research.

Chemical References

• Cancer Vaccines
• Epitopes, T-Lymphocyte
• Immunoglobulin G
• Melanoma-Specific Antigens
• Peptides

Topics

• Amino Acid Sequence
• Antibody Formation (immunology)
• Cancer Vaccines (administration & dosage, immunology)
• Enzyme-Linked Immunosorbent Assay
• Epitopes, T-Lymphocyte (administration & dosage, chemistry, immunology)
• Female
• Humans
• Immunoglobulin G (blood, immunology)
• Kaplan-Meier Estimate
• Male
• Melanoma (immunology, mortality, pathology, therapy)
• Melanoma-Specific Antigens (chemistry, immunology)
• Neoplasm Staging
• Peptides (administration & dosage, chemistry, immunology)
• T-Lymphocyte Subsets (immunology, metabolism)
• T-Lymphocytes, Helper-Inducer (immunology)
• Time Factors
• Treatment Outcome
• Vaccination