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Harnessing Naturally Occurring Tumor Immunity: A Clinical Vaccine Trial in Prostate Cancer

BACKGROUND: Studies of patients with paraneoplastic neurologic disorders (PND) have revealed that apoptotic tumor serves as a potential potent trigger for the initiation of naturally occurring tumor immunity. The purpose of this study was to assess the feasibility, safety, and immunogenicity of an a...

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Autores principales: Frank, Mayu O., Kaufman, Julia, Tian, Suyan, Suárez-Fariñas, Mayte, Parveen, Salina, Blachère, Nathalie E., Morris, Michael J., Slovin, Susan, Scher, Howard I., Albert, Matthew L., Darnell, Robert B.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931687/
https://www.ncbi.nlm.nih.gov/pubmed/20824184
http://dx.doi.org/10.1371/journal.pone.0012367
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author Frank, Mayu O.
Kaufman, Julia
Tian, Suyan
Suárez-Fariñas, Mayte
Parveen, Salina
Blachère, Nathalie E.
Morris, Michael J.
Slovin, Susan
Scher, Howard I.
Albert, Matthew L.
Darnell, Robert B.
author_facet Frank, Mayu O.
Kaufman, Julia
Tian, Suyan
Suárez-Fariñas, Mayte
Parveen, Salina
Blachère, Nathalie E.
Morris, Michael J.
Slovin, Susan
Scher, Howard I.
Albert, Matthew L.
Darnell, Robert B.
author_sort Frank, Mayu O.
collection PubMed
description BACKGROUND: Studies of patients with paraneoplastic neurologic disorders (PND) have revealed that apoptotic tumor serves as a potential potent trigger for the initiation of naturally occurring tumor immunity. The purpose of this study was to assess the feasibility, safety, and immunogenicity of an apoptotic tumor-autologous dendritic cell (DC) vaccine. METHODS AND FINDINGS: We have modeled PND tumor immunity in a clinical trial in which apoptotic allogeneic prostate tumor cells were used to generate an apoptotic tumor-autologous dendritic cell vaccine. Twenty-four prostate cancer patients were immunized in a Phase I, randomized, single-blind, placebo-controlled study to assess the safety and immunogenicity of this vaccine. Vaccinations were safe and well tolerated. Importantly, we also found that the vaccine was immunogenic, inducing delayed type hypersensitivity (DTH) responses and CD4+ and CD8+ T cell proliferation, with no effect on FoxP3+ regulatory T cells. A statistically significant increase in T cell proliferation responses to prostate tumor cells in vitro (p = 0.002), decrease in prostate specific antigen (PSA) slope (p = 0.016), and a two-fold increase in PSA doubling time (p = 0.003) were identified when we compared data before and after vaccination. CONCLUSIONS: An apoptotic cancer cell vaccine modeled on naturally occurring tumor immune responses in PND patients provides a safe and immunogenic tumor vaccine. (ClinicalTrials.gov number NCT00289341). TRIAL REGISTRATION: ClinicalTrials.gov NCT00289341
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spelling pubmed-29316872010-09-03 Harnessing Naturally Occurring Tumor Immunity: A Clinical Vaccine Trial in Prostate Cancer Frank, Mayu O. Kaufman, Julia Tian, Suyan Suárez-Fariñas, Mayte Parveen, Salina Blachère, Nathalie E. Morris, Michael J. Slovin, Susan Scher, Howard I. Albert, Matthew L. Darnell, Robert B. PLoS One Research Article BACKGROUND: Studies of patients with paraneoplastic neurologic disorders (PND) have revealed that apoptotic tumor serves as a potential potent trigger for the initiation of naturally occurring tumor immunity. The purpose of this study was to assess the feasibility, safety, and immunogenicity of an apoptotic tumor-autologous dendritic cell (DC) vaccine. METHODS AND FINDINGS: We have modeled PND tumor immunity in a clinical trial in which apoptotic allogeneic prostate tumor cells were used to generate an apoptotic tumor-autologous dendritic cell vaccine. Twenty-four prostate cancer patients were immunized in a Phase I, randomized, single-blind, placebo-controlled study to assess the safety and immunogenicity of this vaccine. Vaccinations were safe and well tolerated. Importantly, we also found that the vaccine was immunogenic, inducing delayed type hypersensitivity (DTH) responses and CD4+ and CD8+ T cell proliferation, with no effect on FoxP3+ regulatory T cells. A statistically significant increase in T cell proliferation responses to prostate tumor cells in vitro (p = 0.002), decrease in prostate specific antigen (PSA) slope (p = 0.016), and a two-fold increase in PSA doubling time (p = 0.003) were identified when we compared data before and after vaccination. CONCLUSIONS: An apoptotic cancer cell vaccine modeled on naturally occurring tumor immune responses in PND patients provides a safe and immunogenic tumor vaccine. (ClinicalTrials.gov number NCT00289341). TRIAL REGISTRATION: ClinicalTrials.gov NCT00289341 Public Library of Science 2010-09-01 /pmc/articles/PMC2931687/ /pubmed/20824184 http://dx.doi.org/10.1371/journal.pone.0012367 Text en Frank et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Frank, Mayu O.
Kaufman, Julia
Tian, Suyan
Suárez-Fariñas, Mayte
Parveen, Salina
Blachère, Nathalie E.
Morris, Michael J.
Slovin, Susan
Scher, Howard I.
Albert, Matthew L.
Darnell, Robert B.
Harnessing Naturally Occurring Tumor Immunity: A Clinical Vaccine Trial in Prostate Cancer
title Harnessing Naturally Occurring Tumor Immunity: A Clinical Vaccine Trial in Prostate Cancer
title_full Harnessing Naturally Occurring Tumor Immunity: A Clinical Vaccine Trial in Prostate Cancer
title_fullStr Harnessing Naturally Occurring Tumor Immunity: A Clinical Vaccine Trial in Prostate Cancer
title_full_unstemmed Harnessing Naturally Occurring Tumor Immunity: A Clinical Vaccine Trial in Prostate Cancer
title_short Harnessing Naturally Occurring Tumor Immunity: A Clinical Vaccine Trial in Prostate Cancer
title_sort harnessing naturally occurring tumor immunity: a clinical vaccine trial in prostate cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931687/
https://www.ncbi.nlm.nih.gov/pubmed/20824184
http://dx.doi.org/10.1371/journal.pone.0012367
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