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

Journal of Translational Medicine

George Coukos²  Rosemarie Mick¹  Klara Balint²  Greg Motz²  Janos Tanyi²  Cheryl L Chiang²  Lana E Kandalaft² 

[1] Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA;Ovarian Cancer Research Center, University of Pennsylvania, Philadelphia, PA, USA

关键词: Cyclophosphamide;    Bevacizumab;    HOCl;    Tumor vaccine;    Immunotherapy;    Recurrent ovarian cancer;   

Others  :  1205876
DOI  :  10.1186/1479-5876-11-149

 received in 2013-04-17, accepted in 2013-06-12,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Kandalaft et al.; licensee BioMed Central Ltd.

【 图 表 】

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