Multiple costimulatory modalities enhance CTL avidity

James W. Hodge, Mala Chakraborty, Chie Kudo-Saito, Charlie T. Garnett, Jeffrey Schlom

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

Recent studies in both animal models and clinical trials have demonstrated that the avidity of T cells is a major determinant of antitumor and antiviral immunity. In this study, we evaluated several different vaccine strategies for their ability to enhance both the quantity and avidity of CTL responses. CD8+ T cell quantity was measured by tetramer binding precursor frequency, and avidity was measured by both tetramer dissociation and quantitative cytolytic function. We have evaluated a peptide, a viral vector expressing the Ag transgene alone, with one costimulatory molecule (B7-1), and with three costimulatory molecules (B7-1, ICAM-1, and LFA-3), with anti-CTLA-4 mAb, with GM-CSF, and combinations of the above. We have evaluated these strategies in both a foreign Ag model using β-galactosidase as immunogen, and in a "self" Ag model, using carcinoembryonic Ag as immunogen in carcinoembryonic Ag transgenic mice. The combined use of several of these strategies was shown to enhance not only the quantity, but, to a greater magnitude, the avidity of T cells generated; a combination strategy is also shown to enhance antitumor effects. The results reported in this study thus demonstrate multiple strategies that can be used in both antitumor and antiviral vaccine settings to generate higher avidity host T cell responses.

Original languageEnglish
Pages (from-to)5994-6004
Number of pages11
JournalJournal of Immunology
Volume174
Issue number10
Publication statusPublished - 2005 May 15
Externally publishedYes

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CD80 Antigens
T-Lymphocytes
Antiviral Agents
Vaccines
CD58 Antigens
Galactosidases
Intercellular Adhesion Molecule-1
Granulocyte-Macrophage Colony-Stimulating Factor
Transgenes
Transgenic Mice
Immunity
Animal Models
Clinical Trials
Peptides

ASJC Scopus subject areas

  • Immunology

Cite this

Hodge, J. W., Chakraborty, M., Kudo-Saito, C., Garnett, C. T., & Schlom, J. (2005). Multiple costimulatory modalities enhance CTL avidity. Journal of Immunology, 174(10), 5994-6004.

Multiple costimulatory modalities enhance CTL avidity. / Hodge, James W.; Chakraborty, Mala; Kudo-Saito, Chie; Garnett, Charlie T.; Schlom, Jeffrey.

In: Journal of Immunology, Vol. 174, No. 10, 15.05.2005, p. 5994-6004.

Research output: Contribution to journalArticle

Hodge, JW, Chakraborty, M, Kudo-Saito, C, Garnett, CT & Schlom, J 2005, 'Multiple costimulatory modalities enhance CTL avidity', Journal of Immunology, vol. 174, no. 10, pp. 5994-6004.
Hodge JW, Chakraborty M, Kudo-Saito C, Garnett CT, Schlom J. Multiple costimulatory modalities enhance CTL avidity. Journal of Immunology. 2005 May 15;174(10):5994-6004.
Hodge, James W. ; Chakraborty, Mala ; Kudo-Saito, Chie ; Garnett, Charlie T. ; Schlom, Jeffrey. / Multiple costimulatory modalities enhance CTL avidity. In: Journal of Immunology. 2005 ; Vol. 174, No. 10. pp. 5994-6004.
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