A melanoma helper peptide vaccine increases Th1 cytokine production by leukocytes in peripheral blood and immunized lymph nodes. Issue 1 (15th July 2014)

• Record Type: Journal Article
• Authors: Dillon, Patrick M; Olson, Walter C; Czarkowski, Andrea; Petroni, Gina R; Smolkin, Mark; Grosh, William W; Chianese-Bullock, Kimberly A; Deacon, Donna H; Slingluff, Craig L
• Is Part Of: Journal for immunotherapy of cancer. Volume 2:Issue 1(2013)
• Publication Date: 2014-07-15
• Subjects: Immunotherapy -- Human -- Cytokines -- T-Lymphocytes -- Cytotoxic -- Melanoma/im -- Antigens -- Neoplasm -- Tumor vaccines; Cancer -- Immunotherapy -- Periodicals; Cancer -- Immunological aspects -- Periodicals; Tumors -- Immunological aspects -- Periodicals; Immunotherapy -- Periodicals; 616.99406105
• DOI: 10.1186/2051-1426-2-23
• Languages: English
• ISSNs: 2051-1426

Abstract

Abstract : Background: Cancers produce soluble and cell-associated molecules that can suppress or alter antitumor immunity. Preclinical studies suggest the disease burden may alter the cytokine profile of helper T cell responses to cancer antigens. We studied cytokine production by helper T cells responding to vaccination with 6 melanoma helper peptides (6MHP) in blood and lymph nodes. Methods: Twenty-three patients with stage IIIB-IV melanoma received a 6MHP vaccine. Antigen-reactive T cells from blood and draining lymph nodes were cultured, exposed to antigen, and then supernatants (days 2 and 5) were assayed for Th1 and Th2 cytokines. Results from 4 time points were compared to pre-vaccine levels. Results: Cytokine responses to vaccinating peptides were observed in 83% of patients. Th1 favoring responses were most common (17 of 19 responders). The most abundant cytokines produced were IFN-γ and IL-5 in the PBMC's. IL-2 responses predominated in cells obtained from draining lymph nodes in 2-day culture but not in 5-day cultures. Patients with clinically measurable disease produced similar levels of total cytokine and similar degree of Th1 polarization as patients with no evidence of disease (NED). Conclusions: The MHC class II-associated peptides used in this study induced helper T cells with a Th1-biased cytokine response in both PBMC and sentinel immunized nodes. Most patients can mount a Th1 dominant response to these peptides. Future studies are needed to test newer vaccine adjuvants in combination with these peptides. Trial registration: CDR0000378171, Clinicaltrials: NCT00089219 .