A Phase I vaccine trial using dendritic cells pulsed with autologous oxidized lysate for recurrent ovarian cancer.

Details

Ressource 1Download: 1479-5876-11-149.pdf (978.06 [Ko])
State: Public
Version: Final published version
Serval ID
serval:BIB_6E3FA5135726
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Title
A Phase I vaccine trial using dendritic cells pulsed with autologous oxidized lysate for recurrent ovarian cancer.
Journal
Journal of Translational Medicine
Author(s)
Kandalaft L.E., Chiang C.L., Tanyi J., Motz G., Balint K., Mick R., Coukos G.
ISSN
1479-5876 (Electronic)
ISSN-L
1479-5876
Publication state
Published
Issued date
2013
Volume
11
Pages
149
Language
english
Notes
Publication types: Clinical Trial, Phase I ; Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't Publication Status: epublish. pdf type: COMMENTARY
Abstract
PURPOSE: Ovarian cancer, like most solid tumors, is in dire need of effective therapies. The significance of this trial lies in its promise to spearhead the development of combination immunotherapy and to introduce novel approaches to therapeutic immunomodulation, which could enable otherwise ineffective vaccines to achieve clinical efficacy.
RATIONALE: Tumor-infiltrating T cells have been associated with improved outcome in ovarian cancer, suggesting that activation of antitumor immunity will improve survival. However, molecularly defined vaccines have been generally disappointing. Cancer vaccines elicit a modest frequency of low-to-moderate avidity tumor-specific T-cells, but powerful tumor barriers dampen the engraftment, expansion and function of these effector T-cells in the tumor, thus preventing them from reaching their full therapeutic potential. Our work has identified two important barriers in the tumor microenvironment: the blood-tumor barrier, which prevents homing of effector T cells, and T regulatory cells, which inactivate effector T cells. We hypothesize that cancer vaccine therapy will benefit from combinations that attenuate these two barrier mechanisms.
DESIGN: We propose a three-cohort sequential study to investigate a combinatorial approach of a new dendritic cell (DC) vaccine pulsed with autologous whole tumor oxidized lysate, in combination with antiangiogenesis therapy (bevacizumab) and metronomic cyclophosphamide, which impacts Treg cells.
INNOVATION: This study uses a novel autologous tumor vaccine developed with 4-day DCs pulsed with oxidized lysate to elicit antitumor response. Furthermore, the combination of bevacizumab with a whole tumor antigen vaccine has not been tested in the clinic. Finally the combination of bevacizumab and metronomic cyclophosphamide in immunotherapy is novel.
Keywords
Angiogenesis Inhibitors/therapeutic use, Antibodies, Monoclonal, Humanized/therapeutic use, Cancer Vaccines/therapeutic use, Cohort Studies, Cyclophosphamide/administration & dosage, Dendritic Cells/cytology, Fallopian Tube Neoplasms/therapy, Female, Humans, Immunotherapy/methods, Ovarian Neoplasms/therapy, Peritoneal Neoplasms/therapy, Recurrence, Research Design, T-Lymphocytes, Regulatory/immunology
Pubmed
Web of science
Open Access
Yes
Create date
14/10/2014 11:43
Last modification date
20/08/2019 14:27
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