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NY-ESO-1 DNA vaccine induces T-cell responses that are suppressed by regulatory T cells.


ABSTRACT: 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.Eligible patients received treatment with the NY-ESO-1 DNA vaccine. Clinical outcomes and immune responses were assessed.The NY-ESO-1 DNA vaccine was safely administered and induced both antigen-specific effector CD4 and/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 CD4 T-cell responses that were either undetectable pre-vaccine 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 T cells.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.

SUBMITTER: Gnjatic S 

PROVIDER: S-EPMC5806520 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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NY-ESO-1 DNA vaccine induces T-cell responses that are suppressed by regulatory T cells.

Gnjatic Sacha S   Altorki Nasser K NK   Tang Derek Ng DN   Tu Shi-Ming SM   Kundra Vikas V   Ritter Gerd G   Old Lloyd J LJ   Logothetis Christopher J CJ   Sharma Padmanee P  

Clinical cancer research : an official journal of the American Association for Cancer Research 20090310 6


<h4>Purpose</h4>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 pati  ...[more]

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