Combination of p53 Cancer Vaccine with Chemotherapy in Patients with Extensive Stage Small Cell Lung Cancer
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.
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DC-p53 was used as a p53 vaccine with chemotherapy in patients with small cell lung cancer, and objective clinical responses were observed in some patients.
“In researches from Antonia’s and Chiappori’s group, a modified autologous dendritic cells expressing p53 peptides (DC-p53 (254)) was used as a p53 vaccine and applied in combination with chemotherapy in patients with small cell lung cancer (SCLC).595,596 Although objective clinical responses were observed in some patients”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [595]
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- Authors
- Antonia, S. J., Mirza, N., Fricke, I., Chiappori, A., Thompson, P., Williams, N., Bepler, G., Simon, G., Janssen, W., Lee, J.-H., Menander, K., Chada, S., & Gabrilovich, D. I.
- Affiliations
- University of South Florida (US)
- Moffitt Cancer Center (US)
- 3Introgen Therapeutics, Houston, Texas
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2006-02-01
- Volume
- 12
- Issue
- 3
- Pages
- 878-887
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2110530327
- Cited by
- 444
- References
- 44
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 18 · 2023: 9 · 2022: 11 · 2021: 20 · 2020: 26 · 2019: 10 · 2018: 14 · 2017: 23 · 2016: 21 · 2015: 13 · 2014: 26 · 2013: 31 · 2012: 42
- FWCI
- 12.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- dendritic cell vaccine, adenoviral vector, extensive-stage small cell lung cancer, immature myeloid cells, cancer immunotherapy
- MeSH terms
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Combined Modality Therapy, Dendritic Cells, Female, Humans, Immunotherapy, Lung Neoplasms, Male, Middle Aged, Phenotype, T-Lymphocytes, Tumor Suppressor Protein p53, Treatment Outcome, Carcinoma, Small Cell, Cancer Vaccines, Myeloid Cells
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