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Blood, 1 March 2005, Vol. 105, No. 5, pp. 2016-2022.
Prepublished online as a Blood First Edition Paper on September 16, 2004; DOI 10.1182/blood-2004-05-1915.


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Submitted May 19, 2004
Accepted September 3, 2004

Induction of BCR-ABL specific immunity following vaccination with Chaperone Rich Cell Lysates (CRCL) derived from BCR-ABL+ tumor cells

Yi Zeng, Michael W Graner, Sylvia Thompson, Marilyn Marron, and Emmanuel Katsanis*

Department of Pediatrics, Steele Memorial Children's Research Center, University of Arizona, Tucson, AZ, USA

* Corresponding author; email: katsanis{at}peds.arizona.edu.

We have previously reported that chaperone rich cell lysates (CRCL) derived from the BCR-ABL+ 12B1 leukemia activate dendritic cells (DCs) and stimulate leukemia specific immune responses. Since CRCL contain a variety of heat shock/chaperone proteins, we theorized that CRCL obtained from BCR-ABL+ leukemias are likely to chaperone BCR-ABL derived fusion peptides and that DCs pulsed with 12B1 CRCL could cross-present BCR-ABL fusion peptides to T cells. We found that splenocytes from mice vaccinated with BCR-ABL+ leukemia-derived CRCL secreted interferon-{gamma} (IFN-{gamma}) when re-stimulated with a BCR-ABL peptide, GFKQSSKAL, indicating that BCR-ABL peptides are chaperoned by leukemia-derived CRCL. We next eluted peptides from 12B1 leukemia-derived CRCL and used HPLC fractions to re-stimulate splenocytes harvested from mice vaccinated with DC/GFKQSSKAL or DC/12B1 CRCL. We found that the same peptide fractions derived from 12B1 CRCL and from "re-fractionated" GFKQSSKAL stimulated IFN-{gamma} production, suggesting the presence of BCR-ABL peptides in the peptide repertoire of 12B1 CRCL. We also demonstrated that immunization with DCs loaded with leukemia-derived CRCL induced BCR-ABL specific cytotoxic T lymphocytes (CTLs) in vivo. Moreover, mice immunized with DC pulsed with 12B1-derived CRCL had superior survival (60%) when compared to those immunized with DC pulsed with BCR-ABL peptide (20%), indicating that CRCL vaccines provide additional immune stimulus over and above individual peptide vaccination.


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