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Prepublished online as a Blood First Edition Paper on February 6, 2003; DOI 10.1182/blood-2002-10-3108.

Submitted October 15, 2002
Accepted January 22, 2003
Tumor-derived, chaperone-rich cell lysates activate dendritic cells and elicit potent anti-tumor immunity
Yi Zeng, Hanping Feng, Michael W Graner, and Emmanuel Katsanis*
Department of Pediatrics, University of Arizona, Tucson, AZ, USA
* Corresponding author; email: katsanis{at}peds.arizona.edu.
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 positive murine leukemia tumor. We found that DCs incubated with 12B1 derived CRCL had higher expression of CD40 and MHC-II on their cell surface, produced more interleukin-12 (IL-12) and had superior immunostimulatory capacity in a mixed leukocyte reactions (MLR) when compared to 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 over 80% mice rejecting their tumors following a lethal challenge with live 12B1 as compared to 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 are a very effective source of tumor antigen for pulsing DCs. FS-IEF derived CRCL pulsed DCs is a promising anti-cancer vaccine that warrants clinical research and development.

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