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INGN-225: a dendritic cell-based p53 vaccine (Ad.p53-DC) in small cell lung cancer: observed association between immune response and enhanced chemotherapy effect
Open accessAbstract
Importance of the field: Novel approaches are needed for patients with small cell lung cancer (SCLC), as response after relapse is poor with standard therapies. p53 gene mutations often occur, resulting in tumoral protein overexpression and allowing for their recognition by p53-specific cytotoxic T cells.Areas covered in this review: We describe the characteristics and manufacturing of INGN-225, a p53-modified adenovirus-tranduced dendritic cell vaccine, and review available data, to understand INGN-225's role in SCLC treatment. We discuss our pre-clinical, early Phase I/II, and ongoing randomized Phase II studies.What the reader will gain: INGN-225 was well tolerated (all toxicities ≤grade 2) in the Phase I/II trial (54 patients receiving at least 1 dose). Specific anti-p53 immune response was positive in 18/43 (41.8%) patients, with overall post-INGN-225 response observed in 17/33 (51.5%) and immune response data available in 29 (14 positive, 15 negative). Post-INGN-225 response was observed in 11/14 (78.6%) and 5/15 (33%) patients with positive and negative immune responses, respectively.Take home message: INGN-225 is safe, induces a significant immune response, and appears to sensitize SCLC to subsequent chemotherapy. Improvements in immune response induction and understanding the chemotherapy–immunotherapy synergism will determine INGN-225's future role as an anticancer therapy.
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“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 [596]
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Metadata
- Authors
- Chiappori, A. A., Soliman, H., Janssen, W. E., Antonia, S. J., & Gabrilovich, D. I.
- Affiliations
- University of South Florida (US)
- Moffitt Cancer Center (US)
- Corresponding author
- Chiappori, Alberto A
- Venue
- Expert Opinion on Biological Therapy
- Publisher
- Informa UK Limited
- Published
- 2010-04-26
- Volume
- 10
- Issue
- 6
- Pages
- 983-991
- ISSN
- 1471-2598 (ISSN-L)
- 1744-7682
- PMC
- PMC3146364
- OpenAlex
- W2144694610
- Cited by
- 126
- References
- 61
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 6 · 2023: 6 · 2022: 6 · 2021: 10 · 2020: 4 · 2019: 6 · 2018: 7 · 2017: 6 · 2016: 12 · 2015: 10 · 2014: 10 · 2013: 9 · 2012: 11
- FWCI
- 4.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Expert Opinion on Biological Therapy (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (K24CA128953, P50CA119997)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- dendritic cell vaccine, p53, small cell lung cancer, adenoviral vector, cancer immunotherapy, chemosensitization, vaccine safety, TP53 mutation
- MeSH terms
- Animals, Dendritic Cells, Humans, Immunotherapy, Lung Neoplasms, Randomized Controlled Trials as Topic, Tumor Suppressor Protein p53, Clinical Trials, Phase I as Topic, Clinical Trials, Phase II as Topic, Cancer Vaccines, Small Cell Lung Carcinoma
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