A dendritic cell vaccine pulsed with autologous hypochlorous Acid-oxidized ovarian cancer lysate primes effective broad antitumor immunity: from bench to bedside.

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Serval ID
serval:BIB_2509A0717B99
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A dendritic cell vaccine pulsed with autologous hypochlorous Acid-oxidized ovarian cancer lysate primes effective broad antitumor immunity: from bench to bedside.
Journal
Clinical Cancer Research
Author(s)
Chiang C.L., Kandalaft L.E., Tanyi J., Hagemann A.R., Motz G.T., Svoronos N., Montone K., Mantia-Smaldone G.M., Smith L., Nisenbaum H.L., Levine B.L., Kalos M., Czerniecki B.J., Torigian D.A., Powell D.J., Mick R., Coukos G.
ISSN
1078-0432 (Print)
ISSN-L
1078-0432
Publication state
Published
Issued date
2013
Peer-reviewed
Oui
Volume
19
Number
17
Pages
4801-4815
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish
Abstract
PURPOSE: Whole tumor lysates are promising antigen sources for dendritic cell (DC) therapy as they contain many relevant immunogenic epitopes to help prevent tumor escape. Two common methods of tumor lysate preparations are freeze-thaw processing and UVB irradiation to induce necrosis and apoptosis, respectively. Hypochlorous acid (HOCl) oxidation is a new method for inducing primary necrosis and enhancing the immunogenicity of tumor cells.
EXPERIMENTAL DESIGN: We compared the ability of DCs to engulf three different tumor lysate preparations, produce T-helper 1 (TH1)-priming cytokines and chemokines, stimulate mixed leukocyte reactions (MLR), and finally elicit T-cell responses capable of controlling tumor growth in vivo.
RESULTS: We showed that DCs engulfed HOCl-oxidized lysate most efficiently stimulated robust MLRs, and elicited strong tumor-specific IFN-γ secretions in autologous T cells. These DCs produced the highest levels of TH1-priming cytokines and chemokines, including interleukin (IL)-12. Mice vaccinated with HOCl-oxidized ID8-ova lysate-pulsed DCs developed T-cell responses that effectively controlled tumor growth. Safety, immunogenicity of autologous DCs pulsed with HOCl-oxidized autologous tumor lysate (OCDC vaccine), clinical efficacy, and progression-free survival (PFS) were evaluated in a pilot study of five subjects with recurrent ovarian cancer. OCDC vaccination produced few grade 1 toxicities and elicited potent T-cell responses against known ovarian tumor antigens. Circulating regulatory T cells and serum IL-10 were also reduced. Two subjects experienced durable PFS of 24 months or more after OCDC.
CONCLUSIONS: This is the first study showing the potential efficacy of a DC vaccine pulsed with HOCl-oxidized tumor lysate, a novel approach in preparing DC vaccine that is potentially applicable to many cancers. Clin Cancer Res; 19(17); 4801-15. ©2013 AACR.
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Create date
03/10/2013 17:01
Last modification date
20/08/2019 13:03
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