Journal
JOURNAL FOR IMMUNOTHERAPY OF CANCER
Volume 2, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/2051-1426-2-23
Keywords
Immunotherapy; Human; Cytokines; T-Lymphocytes; Cytotoxic; Melanoma/im; Antigens; Neoplasm; Tumor vaccines
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Funding
- NIH/NCI [R21 CA105777, U01 CA1/8846]
- University of Virginia Cancer Center Support Grant [NIH/NCI P30 CA44579]
- UVA General Clinical Research Center [NIH M01 RR00847]
- Commonwealth Foundation for Cancer Research
- Alice and Bill Goodwin
- University of Virginia
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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-gamma 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 Thi dominant response to these peptides. Future studies are needed to test newer vaccine adjuvants in combination with these peptides.
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