Effect of montanide and Poly-ICLC adjuvant on human self/tumor antigen-specific CD4(+) T cells in phase I overlapping long peptide vaccine trial Journal Article
| Authors: | Tsuji, T.; Sabbatini, P.; Jungbluth, A. A.; Ritter, E.; Pan, L.; Ritter, G.; Ferran, L.; Spriggs, D.; Salazar, A. M.; Gnjatic, S. |
| Article Title: | Effect of montanide and Poly-ICLC adjuvant on human self/tumor antigen-specific CD4(+) T cells in phase I overlapping long peptide vaccine trial |
| Abstract: | Vaccination of patients with ovarian cancer with overlapping long peptides (OLP) from cancer-testis antigen NY-ESO-1 and poly-ICLC in Montanide-ISA-51 (Montanide) was found to consistently induce integrated immune responses (antibody, CD4(+), and CD8(+) T cells). Using detailed methods, we investigated the respective effects of poly-ICLC and Montanide adjuvant on pre- and postvaccine NY-ESO-1-specific CD4(+) T cells, because of their central function for induction and maintenance of both antibody and CD8(+) T cells. Polyclonal NY-ESO-1-specific CD4(+) T-cell lines were generated from 12 patients using CD154-based selection of precursors before and after vaccination with (i) OLP alone, (ii) OLP in Montanide, or (iii) OLP and poly-ICLC in Montanide. Kinetics, quantification, fine specificity, avidity, and cytokine-producing pattern were analyzed in depth and compared between vaccine cohorts. Vaccination with OLP alone did not elicit CD4(+) T-cell responses; it suppressed high-avidity CD4(+) T-cell precursors that recognized naturally processed NY-ESO-1 protein before vaccination. Emulsification of OLP in Montanide was required for the expansion of high-avidity NY-ESO-1-specific CD4(+) T-cell precursors. Poly-ICLC significantly enhanced CD4(+) Th1 responses while suppressing the induction of interleukin (IL)-4-producing Th2 and IL-9-producing Th9 cells. In summary, Montanide and poly-ICLC had distinct and cooperative effects for the induction of NY-ESO-1-specific Th1 cells and integrated immune responses by OLP vaccination. These results support the use of admixing poly-ICLC in Montanide adjuvant to rapidly induce antitumor type I immune responses by OLP from self/tumor antigens in human cancer vaccines. (C) 2013 AACR. |
| Keywords: | protein; tolerance; cancer-patients; cells; immune-responses; cd8(+); induction; tumor-immunity; dendritic; double-stranded-rna; toll-like receptor-3 |
| Journal Title: | Cancer Immunology Research |
| Volume: | 1 |
| Issue: | 5 |
| ISSN: | 2326-6066 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2013-11-01 |
| Start Page: | 340 |
| End Page: | 350 |
| Language: | English |
| ACCESSION: | WOS:000340030400010 |
| DOI: | 10.1158/2326-6066.cir-13-0089 |
| PROVIDER: | wos |
| PUBMED: | 24777970 |
| Notes: | Article -- Source: Wos |
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