Harnessing naturally occurring tumor immunity: A clinical vaccine trial in prostate cancer Journal Article
| Authors: | Frank, M. O.; Kaufman, J.; Tian, S.; Suärez-Farïas, M.; Parveen, S.; Blachere, N. E.; Morris, M. J.; Slovin, S.; Scher, H. I.; Albert, M. L.; Darnell, R. B. |
| Article Title: | Harnessing naturally occurring tumor immunity: A clinical vaccine trial in prostate cancer |
| Abstract: | 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). © 2010 Frank et al. |
| Keywords: | adult; clinical article; controlled study; aged; aged, 80 and over; middle aged; human cell; clinical trial; drug tolerability; placebo; drug efficacy; drug safety; transcription factor foxp3; cd8+ t lymphocyte; lymphocyte proliferation; prostate specific antigen; cytology; dendritic cell vaccine; apoptosis; controlled clinical trial; dendritic cell; randomized controlled trial; cell line, tumor; transplantation; injection site reaction; prostate cancer; prostate-specific antigen; prostatic neoplasms; regulatory t lymphocyte; immunology; dendritic cells; feasibility study; immune response; cancer vaccine; cancer vaccines; immunogenicity; cancer cell; prostate tumor; cd4+ t lymphocyte; vaccination; tumor cell line; tumor immunity; phase 1 clinical trial; biological therapy; single blind procedure; delayed hypersensitivity; tissue therapy |
| Journal Title: | PLoS ONE |
| Volume: | 5 |
| Issue: | 9 |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Date Published: | 2010-09-01 |
| Start Page: | e12367 |
| Language: | English |
| DOI: | 10.1371/journal.pone.0012367 |
| PUBMED: | 20824184 |
| PROVIDER: | scopus |
| PMCID: | PMC2931687 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 20 April 2011" - "Art. No.: e12367" - "Source: Scopus" |
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