A melanoma helper peptide vaccine increases Th1 cytokine production by leukocytes in peripheral blood and immunized lymph nodes.

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.

• Authors: Patrick M Dillon, Walter C Olson, Andrea Czarkowski, Gina R Petroni, Mark Smolkin, William W Grosh, Kimberly A Chianese-Bullock, Donna H Deacon, Craig L Slingluff Jr
• Journal: Journal for immunotherapy of cancer (J Immunother Cancer) Vol. 2 Pg. 23 ( 2014) ISSN: 2051-1426 [Print] England
• PMID: 25126421 (Publication Type: Journal Article)