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A phase-1/2 study of adenovirus-p53 transduced dendritic cell vaccine in combination with indoximod in metastatic solid tumors and invasive breast cancer

BACKGROUND: Indoleamine 2, 3-dioxygenase is an enzyme that causes immunosuppression in tumors. Indoximod inhibits the indoleamine 2, 3-dioxygenase pathway and enhances immunologic responses to dendritic cell (DC) vaccines preclinically. Adenovirus p53 (Ad.p53) is used to generate DC vaccines against...

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Autores principales: Soliman, Hatem, Khambati, Fatema, Han, Hyo S., Ismail-Khan, Roohi, Bui, Marilyn M., Sullivan, Daniel M., Antonia, Scott
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839376/
https://www.ncbi.nlm.nih.gov/pubmed/29515795
http://dx.doi.org/10.18632/oncotarget.24118
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author Soliman, Hatem
Khambati, Fatema
Han, Hyo S.
Ismail-Khan, Roohi
Bui, Marilyn M.
Sullivan, Daniel M.
Antonia, Scott
author_facet Soliman, Hatem
Khambati, Fatema
Han, Hyo S.
Ismail-Khan, Roohi
Bui, Marilyn M.
Sullivan, Daniel M.
Antonia, Scott
author_sort Soliman, Hatem
collection PubMed
description BACKGROUND: Indoleamine 2, 3-dioxygenase is an enzyme that causes immunosuppression in tumors. Indoximod inhibits the indoleamine 2, 3-dioxygenase pathway and enhances immunologic responses to dendritic cell (DC) vaccines preclinically. Adenovirus p53 (Ad.p53) is used to generate DC vaccines against p53. A phase-1/2 trial of indoximod with Ad.p53-DC vaccine was conducted. MATERIALS AND METHODS: The phase-1 study combined 7 indoximod dose levels with < 6 Ad.p53-DC vaccinations every 2 weeks. Primary endpoints were maximum-tolerated dose in phase 1 and objective response in phase 2. Flow cytometry measured immune responses. RESULTS: Thirty-nine patients were treated. In combination with Ad.p53-DC vaccine, the maximum-tolerated dose of indoximod was 1600 mg twice daily. Attributable toxicities were grade 1–2. Best response was stable disease in 4 patients. Immunologic responses were detected in 7 out of 23 evaluable patients. Median progression-free survival was 13.3 weeks (95% confidence interval, 12.97–21.85) and median overall survival was 20.71 weeks (95% confidence interval, 25.75–46.15). Nine out of 22 patients (40%) benefitted from chemotherapy after vaccination. Median overall survival in chemotherapy responders was 69.4 weeks (30.1–122.1). CONCLUSIONS: Indoximod 1600 mg twice daily with Ad.p53-DC was well tolerated. There may have been a chemosensitization effect. Future trials should explore combining this treatment with chemotherapy.
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spelling pubmed-58393762018-03-07 A phase-1/2 study of adenovirus-p53 transduced dendritic cell vaccine in combination with indoximod in metastatic solid tumors and invasive breast cancer Soliman, Hatem Khambati, Fatema Han, Hyo S. Ismail-Khan, Roohi Bui, Marilyn M. Sullivan, Daniel M. Antonia, Scott Oncotarget Clinical Research Paper BACKGROUND: Indoleamine 2, 3-dioxygenase is an enzyme that causes immunosuppression in tumors. Indoximod inhibits the indoleamine 2, 3-dioxygenase pathway and enhances immunologic responses to dendritic cell (DC) vaccines preclinically. Adenovirus p53 (Ad.p53) is used to generate DC vaccines against p53. A phase-1/2 trial of indoximod with Ad.p53-DC vaccine was conducted. MATERIALS AND METHODS: The phase-1 study combined 7 indoximod dose levels with < 6 Ad.p53-DC vaccinations every 2 weeks. Primary endpoints were maximum-tolerated dose in phase 1 and objective response in phase 2. Flow cytometry measured immune responses. RESULTS: Thirty-nine patients were treated. In combination with Ad.p53-DC vaccine, the maximum-tolerated dose of indoximod was 1600 mg twice daily. Attributable toxicities were grade 1–2. Best response was stable disease in 4 patients. Immunologic responses were detected in 7 out of 23 evaluable patients. Median progression-free survival was 13.3 weeks (95% confidence interval, 12.97–21.85) and median overall survival was 20.71 weeks (95% confidence interval, 25.75–46.15). Nine out of 22 patients (40%) benefitted from chemotherapy after vaccination. Median overall survival in chemotherapy responders was 69.4 weeks (30.1–122.1). CONCLUSIONS: Indoximod 1600 mg twice daily with Ad.p53-DC was well tolerated. There may have been a chemosensitization effect. Future trials should explore combining this treatment with chemotherapy. Impact Journals LLC 2018-01-10 /pmc/articles/PMC5839376/ /pubmed/29515795 http://dx.doi.org/10.18632/oncotarget.24118 Text en Copyright: © 2018 Soliman et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Clinical Research Paper
Soliman, Hatem
Khambati, Fatema
Han, Hyo S.
Ismail-Khan, Roohi
Bui, Marilyn M.
Sullivan, Daniel M.
Antonia, Scott
A phase-1/2 study of adenovirus-p53 transduced dendritic cell vaccine in combination with indoximod in metastatic solid tumors and invasive breast cancer
title A phase-1/2 study of adenovirus-p53 transduced dendritic cell vaccine in combination with indoximod in metastatic solid tumors and invasive breast cancer
title_full A phase-1/2 study of adenovirus-p53 transduced dendritic cell vaccine in combination with indoximod in metastatic solid tumors and invasive breast cancer
title_fullStr A phase-1/2 study of adenovirus-p53 transduced dendritic cell vaccine in combination with indoximod in metastatic solid tumors and invasive breast cancer
title_full_unstemmed A phase-1/2 study of adenovirus-p53 transduced dendritic cell vaccine in combination with indoximod in metastatic solid tumors and invasive breast cancer
title_short A phase-1/2 study of adenovirus-p53 transduced dendritic cell vaccine in combination with indoximod in metastatic solid tumors and invasive breast cancer
title_sort phase-1/2 study of adenovirus-p53 transduced dendritic cell vaccine in combination with indoximod in metastatic solid tumors and invasive breast cancer
topic Clinical Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839376/
https://www.ncbi.nlm.nih.gov/pubmed/29515795
http://dx.doi.org/10.18632/oncotarget.24118
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