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Recognition of live phosphatidylserine-labeled tumor cells by dendritic cells: a novel approach to immunotherapy of skin cancer.

Authors
Shurin-MR; Potapovich-AI; Tyurina-YY; Tourkova-IL; Shurin-GV; Kagan-VE
Source
Cancer Res 2009 Mar; 69(6):2487-2496
NIOSHTIC No.
20035415
Abstract
Dendritic cells (DC) loaded with tumor antigens from apoptotic/necrotic tumor cells are commonly used as vaccines for cancer therapy. However, the use of dead tumor cells may cause both tolerance and immunity, making the effect of vaccination unpredictable. To deliver live tumor ''cargoes'' into DC, we developed a new approach based on the ''labeling'' of tumors with a phospholipid ''eat-me'' signal, phosphatidylserine. Expression of phosphatidylserine on live tumor cells mediated their recognition and endocytosis by DC resulting in the presentation of tumor antigens to antigen-specific T cells. In mice, topical application of phosphatidylserine-containing ointment over melanoma induced tumor-specific CTL, local and systemic antitumor immunity, and inhibited tumor growth. Thus, labeling of tumors with phosphatidylserine is a promising strategy for cancer immunotherapy.
Keywords
Biochemical-indicators; Biological-effects; Biological-factors; Biological-monitoring; Biomarkers; Cancer; Cell-biology; Cellular-reactions; Cytology; Exposure-assessment; Exposure-levels; Exposure-methods; Immune-reaction; Immunology; Immunotoxins Laboratory-animals; Microscopic-analysis; Microscopy; Skin-cancer; Statistical-analysis; Toxic-effects; Tumor-inhibition; Tumors; Author Keywords: Phosphatidylserine; Dendritic cells; Melanoma; Lymphoma; Topical therapy; Apoptosis; Necrosis; Endocytosis
Contact
Valerian E. Kagan or Michael R. Shurin, Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA
CODEN
CNREA8
Publication Date
20090315
Document Type
Journal Article
Email Address
kagan@pitt.edu; shurinmr@upmc.edu
Funding Type
Grant
Fiscal Year
2009
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-008282
Issue of Publication
6
ISSN
0008-5472
NIOSH Division
HELD
Priority Area
Manufacturing
Source Name
Cancer Research
State
PA; WV; OH
Performing Organization
University of Pittsburgh at Pittsburgh
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