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

Authors: Gnjatic, S.; Altorki, N. K.; Ngtang, D.; Tu, S. M.; Kundra, V.; Ritter, G.; Old, L. J.; Logothetis, C. J.; Sharma, P.
Article Title: NY-ESO-1 DNA vaccine induces T-Cell responses that are suppressed by regulatory T Cells
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. © 2009 American Association for Cancer Research.
Keywords: clinical article; unclassified drug; human cell; neoplasms; t lymphocyte; lung non small cell cancer; membrane proteins; cancer regression; regulatory t lymphocyte; immune response; amino acid sequence; molecular sequence data; antigens, neoplasm; cancer vaccines; t-lymphocytes, regulatory; ny eso 1 antigen; cd4+ t lymphocyte; cd4-positive t-lymphocytes; vaccination; remission; dna vaccine; prostate adenocarcinoma; ny eso 1 dna vaccine; cell activity; esophagus carcinoma; injection site erythema; vaccines, dna
Journal Title: Clinical Cancer Research
Volume: 15
Issue: 6
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2009-03-15
Start Page: 2130
End Page: 2139
Language: English
DOI: 10.1158/1078-0432.ccr-08-2632
PUBMED: 19276258
PROVIDER: scopus
PMCID: PMC5806520
Notes: --- - "Cited By (since 1996): 13" - "Export Date: 30 November 2010" - "CODEN: CCREF" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Sacha Gnjatic
    111 Gnjatic
  2. Gerd Ritter
    158 Ritter
  3. Lloyd J Old
    386 Old