NY-ESO-1 DNA vaccine induces T-Cell responses that are suppressed by regulatory T Cells

Sacha Gnjatic, Nasser K. Altorki, Derek Ngtang, Shi Ming Tu, Vikas Kundra, Gerd Ritter, Lloyd J. Old, Christopher J. Logothetis, Padmanee Sharma

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

Purpose: Different vaccination strategies against the NY-ESO-1 antigen have been employed in an attempt to induce antitumor immune responses. Antigen-specific effector T-cell responses have been reported in a subset of vaccinated patients; however, these responses have not consistently correlated with disease regression. Here, we report for the first time clinical and immune responses generated by the NY-ESO-1 DNA vaccine administered by particle-mediated epidermal delivery to cancer patients. Experimental Design: Eligible patients received treatment with the NY-ESO-1 DNA vaccine. Clinical outcomes and immune responses were assessed. Results: The NY-ESO-1 DNA vaccine was safely administered and induced both antigen-specific effector CD4and/or CD8 T-cell responses in 93% (14 of 15) of patients who did not have detectable pre-vaccine immune responses. Despite the induction of antigen-specific T-cell responses, clinical outcomes consisted predominantly of progressive disease. Detectable effector T-cell responses were inconsistent and did not persist in all patients after completion of the scheduled vaccinations. However, high-avidity CD4T-cell responses that were either undetectable prevaccine or found to be diminished at a later time during the clinical trial were detected in certain patients'samples after in vitro depletion of regulatory Tcells. Conclusions: Regulatory T cells play a role in diminishing vaccine-induced antigen-specific effector T-cell responses in cancer patients. The NY-ESO-1 DNA vaccine represents a feasible immunotherapeutic strategy to induce antigen-specific T-cell responses. Counteracting regulatory T-cell activity before vaccination may lead to prolonged effector T-cell responses and possibly antitumor responses in cancer patients.

Original languageEnglish
Pages (from-to)2130-2139
Number of pages10
JournalClinical Cancer Research
Volume15
Issue number6
DOIs
StatePublished - 15 Mar 2009
Externally publishedYes

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