Effect of Montanide and poly-ICLC adjuvant on human self/tumor antigen-specific CD4+ T cells in phase I overlapping long peptide vaccine trial Academic Article uri icon

Overview

MeSH Major

  • CD4-Positive T-Lymphocytes
  • Cancer Vaccines
  • Carboxymethylcellulose Sodium
  • Mannitol
  • Oleic Acids
  • Peptides
  • Poly I-C
  • Polylysine

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.

publication date

  • November 2013

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1158/2326-6066.CIR-13-0089

PubMed ID

  • 24777970

Additional Document Info

start page

  • 340

end page

  • 50

volume

  • 1

number

  • 5