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Prepublished online as a Blood First Edition Paper on February 6, 2003; DOI 10.1182/blood-2002-10-3108. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-10-3108v1 101/11/4485    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zeng, Y. Articles by Katsanis, E. Search for Related Content PubMed PubMed Citation Articles by Zeng, Y. Articles by Katsanis, E. Related Collections Immunobiology Neoplasia Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 June 2003, Vol. 101, No. 11, pp. 4485-4491 IMMUNOBIOLOGY Tumor-derived, chaperone-rich cell lysate activates dendritic cells and elicits potent antitumor immunity Yi Zeng, Hanping Feng, Michael W. Graner, and Emmanuel Katsanis From the Department of Pediatrics, Steele Memorial Children's Research Center, University of Arizona, Tucson, AZ. We have utilized a free-solution isoelectric focusing technique (FS-IEF) to obtain chaperone-rich cell lysate (CRCL) fractions from clarified tumor homogenates and have previously reported on their vaccinating potential. To better understand the underlying mechanisms as well as to improve on the immunizing efficacy of tumor-derived chaperone complexes, in the present study we examined the effects of CRCL-loaded dendritic cells (DCs) against 12B1, an aggressive bcr-abl+ murine leukemia tumor. We found that DCs incubated with 12B1-derived CRCL had higher expression of CD40 and major histocompatibility complex class II (MHC-II) on their cell surface, produced more interleukin-12 (IL-12), and had superior immunostimulatory capacity in a mixed leukocyte reaction (MLR) when compared with DCs exposed to unfractionated tumor lysate or purified heat-shock protein 70 (HSP70). Vaccination of mice with 12B1 CRCL–pulsed DCs significantly prolonged their survival, with more than 80% of mice rejecting their tumors following a lethal challenge with live 12B1 compared with those immunized with tumor lysate or HSP70-loaded DCs. The protective immunity generated was tumor specific, long lasting, and both CD4+ and CD8+ T-cell dependent. Moreover, immunization with CRCL-loaded DCs resulted in a 75% cure rate in mice with pre-existing 12B1 tumors. Our findings indicate that CRCL has prominent adjuvant effects and is a very effective source of tumor antigen for pulsing DCs. FS-IEF–derived CRCL-pulsed DCs are a promising anticancer vaccine that warrants clinical research and development. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. Larmonier, N. Janikashvili, C. J. LaCasse, C. B. Larmonier, J. Cantrell, E. Situ, T. Lundeen, B. Bonnotte, and E. Katsanis Imatinib Mesylate Inhibits CD4+CD25+ Regulatory T Cell Activity and Enhances Active Immunotherapy against BCR-ABL- Tumors J. Immunol., November 15, 2008; 181(10): 6955 - 6963. [Abstract] [Full Text] [PDF] N. Larmonier, J. Cantrell, C. LaCasse, G. Li, N. Janikashvili, E. Situ, M. Sepassi, S. Andreansky, and E. Katsanis Chaperone-rich tumor cell lysate-mediated activation of antigen-presenting cells resists regulatory T cell suppression J. Leukoc. Biol., April 1, 2008; 83(4): 1049 - 1059. [Abstract] [Full Text] [PDF] G. Li, S. Andreansky, G. Helguera, M. Sepassi, N. Janikashvili, J. Cantrell, C. L. LaCasse, N. Larmonier, M. L. Penichet, and E. Katsanis A chaperone protein-enriched tumor cell lysate vaccine generates protective humoral immunity in a mouse breast cancer model Mol. Cancer Ther., March 1, 2008; 7(3): 721 - 729. [Abstract] [Full Text] [PDF] M. W. Graner, R. I. Cumming, and D. D. Bigner The Heat Shock Response and Chaperones/Heat Shock Proteins in Brain Tumors: Surface Expression, Release, and Possible Immune Consequences J. Neurosci., October 17, 2007; 27(42): 11214 - 11227. [Abstract] [Full Text] [PDF] K. L. Kislin, M. T. Marron, G. Li, M. W. Graner, and E. Katsanis Chaperone-rich cell lysate embedded with BCR-ABL peptide demonstrates enhanced anti-tumor activity against a murine BCR-ABL positive leukemia FASEB J, July 1, 2007; 21(9): 2173 - 2184. [Abstract] [Full Text] [PDF] A. Clayton, A. Turkes, H. Navabi, M. D. Mason, and Z. Tabi Induction of heat shock proteins in B-cell exosomes J. Cell Sci., August 15, 2005; 118(16): 3631 - 3638. [Abstract] [Full Text] [PDF] M. W. Graner and D. D. Bigner Chaperone proteins and brain tumors: Potential targets and possible therapeutics Neuro-oncol, July 1, 2005; 7(3): 260 - 278. [Abstract] [PDF] Y. Zeng, M. W. Graner, S. Thompson, M. Marron, and E. Katsanis Induction of BCR-ABL-specific immunity following vaccination with chaperone-rich cell lysates derived from BCR-ABL+ tumor cells Blood, March 1, 2005; 105(5): 2016 - 2022. [Abstract] [Full Text] [PDF] M. W. Graner, A. Likhacheva, J. Davis, A. Raymond, J. Brandenberger, A. Romanoski, S. Thompson, E. Akporiaye, and E. Katsanis Cargo from Tumor-Expressed Albumin Inhibits T-Cell Activation and Responses Cancer Res., November 1, 2004; 64(21): 8085 - 8092. [Abstract] [Full Text] [PDF]

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