CD4-Directed Peptide Vaccination Augments an Antitumor Response, but Efficacy Is Limited by the Number of CD8+ T Cell Precursors

Holly L. Hanson, Sylvia Kang, Lyse A. Norian, Ken Matsui, Leigh A. O'Mara, Paul M. Allen

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Peptide vaccination is an immunotherapeutic strategy being pursued as a method of enhancing Ag-specific antitumor responses. To date, most studies have focused on the use of MHC class I-restricted peptides, and have not shown a correlation between Ag-specific CD8+ T cell expansion and the generation of protective immune responses. We investigated the effects of CD4-directed peptide vaccination on the ability of CD8+ T cells to mount protective antitumor responses in the DUC18/CMS5 tumor model system. To accomplish this, we extended the amino acid sequence of the known MHC class I-restricted DUC18 rejection epitope from CMS5 to allow binding to MHC class II molecules. Immunization with this peptide (tumor-derived extracellular signal-regulated kinase-II (tERK-II)) induced Ag-specific CD4+ T cell effector function, but did not directly prime CD8+ T cells. Approximately 31% of BALB/c mice immunized with tERK-II were protected from subsequent tumor challenge in a CD40-dependent manner. Priming of endogenous CD8+ T cells in immunized mice was detected only after CMS5 challenge. Heightened CD4+ Th cell function in response to tERK II vaccination allowed a 12-fold reduction in the number of adoptively transferred CD8+ DUC18 T cells needed to protect recipients against tumor challenge as compared with previous studies using unimmunized mice. Furthermore, tERK-II immunization led to a more rapid and transient expansion of transferred DUC18 T cells than was seen in unimmunized mice. These findings illustrate that CD4-directed peptide vaccination augments antitumor immunity, but that the number of tumor-specific precursor CD8+ T cells will ultimately dictate the success of immunotherapy.

Original languageEnglish (US)
Pages (from-to)4215-4224
Number of pages10
JournalJournal of Immunology
Volume172
Issue number7
StatePublished - Apr 1 2004
Externally publishedYes

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T-Lymphoid Precursor Cells
Vaccination
T-Lymphocytes
Peptides
Extracellular Signal-Regulated MAP Kinases
Neoplasms
Immunization
Immunotherapy
Epitopes
Amino Acid Sequence
Immunity

ASJC Scopus subject areas

  • Immunology

Cite this

CD4-Directed Peptide Vaccination Augments an Antitumor Response, but Efficacy Is Limited by the Number of CD8+ T Cell Precursors. / Hanson, Holly L.; Kang, Sylvia; Norian, Lyse A.; Matsui, Ken; O'Mara, Leigh A.; Allen, Paul M.

In: Journal of Immunology, Vol. 172, No. 7, 01.04.2004, p. 4215-4224.

Research output: Contribution to journalArticle

Hanson, Holly L. ; Kang, Sylvia ; Norian, Lyse A. ; Matsui, Ken ; O'Mara, Leigh A. ; Allen, Paul M. / CD4-Directed Peptide Vaccination Augments an Antitumor Response, but Efficacy Is Limited by the Number of CD8+ T Cell Precursors. In: Journal of Immunology. 2004 ; Vol. 172, No. 7. pp. 4215-4224.
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