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Clin Cancer Res. 2006 Feb 1;12(3 Pt 1):878-87.

Combination of p53 cancer vaccine with chemotherapy in patients with extensive stage small cell lung cancer.

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1
H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA.

Abstract

PURPOSE:

The initial goal of this study was to test the immunologic and clinical effects of a new cancer vaccine consisting of dendritic cells (DC) transduced with the full-length wild-type p53 gene delivered via an adenoviral vector in patients with extensive stage small cell lung cancer.

EXPERIMENTAL DESIGN:

Twenty-nine patients with extensive stage small cell lung cancer were vaccinated repeatedly at 2-week intervals. Most of the patients received three immunizations. p53-specific responses were evaluated, and phenotype and function of T cells, DCs, and immature myeloid cells were analyzed and correlated with antigen-specific immune responses. Objective clinical response to vaccination as well as subsequent chemotherapy was evaluated.

RESULTS:

p53-specific T cell responses to vaccination were observed in 57.1% of patients. Immunologic responses to vaccination were positively associated with a moderate increase in the titer of antiadenovirus antibodies, and negatively with an accumulation of immature myeloid cells. One patient showed a clinical response to vaccination whereas most of the patients had disease progression. However, we observed a high rate of objective clinical responses to chemotherapy (61.9%) that immediately followed vaccination. Clinical response to subsequent chemotherapy was closely associated with induction of immunologic response to vaccination.

CONCLUSIONS:

This study provides clinical support for an emerging paradigm in cancer immunotherapy, wherein optimal use of vaccination might be more effective, not as a separate modality, but in direct combination with chemotherapy.

PMID:
16467102
DOI:
10.1158/1078-0432.CCR-05-2013
[Indexed for MEDLINE]
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