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Cancer Therapy: Clinical |
Authors' Affiliations: 1 H. Lee Moffitt Cancer Center and Research Institute, 2 Department of Interdisciplinary Oncology, University of South Florida, Tampa, Florida, and 3 Introgen Therapeutics, Houston, Texas
Requests for reprints: Dmitry Gabrilovich, Department of Interdisciplinary Oncology, University of South Florida, MRC, Room 2067, 12902 Magnolia Drive, Tampa, FL 33612. Phone: 813-903-6863; Fax: 813-632-1328; E-mail: dgabril{at}moffitt.usf.edu.
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.
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