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Chaperone-rich cell lysate embedded with BCR-ABL peptide demonstrates enhanced anti-tumor activity against a murine BCR-ABL positive leukemia

Kerri L. Kislin^*,, Marilyn T. Marron, Gang Li, Michael W. Graner^,1,2 and Emmanuel Katsanis^,1

^* Cancer Biology Interdisciplinary Program, University of Arizona, Tucson, Arizona, USA;

Duke University Medical Center, Durham, North Carolina, USA; and

Steele Children’s Research Center, University of Arizona, Tucson Arizona, USA

²Correspondence: Duke University Medical Center, Pathology/Preston Robert Tisch Brain Tumor Center at Duke, Box 3156, Medical Sciences Research Bldg. 173A, Durham, NC 27710, USA. E-mail: michael.graner{at}duke.edu

Chaperone proteins are effective antitumor vaccines when purified from a tumor source, some of which are in clinical trials. Such vaccines culminate in tumor-specific T cell responses, implicating the role of adaptive immunity. We have developed a rapid and efficient procedure utilizing an isoelectric focusing technique to obtain vaccines from tumor or normal tissues called chaperone-rich cell lysate (CRCL). Tumor-associated peptides, the currency of T cell-mediated anticancer immunity, are believed to be purveyed by chaperone vaccines. Our purpose was to demonstrate our ability to manipulate the peptide antigen repertoire of CRCL vaccines as a novel anticancer strategy. Our methods allow us to prepare "designer" CRCL, utilizing the immunostimulation activity and the carrying capacity of CRCL to quantitatively acquire and deliver exogenous antigenic peptides (e.g., derived from the oncogenic BCR/ABL protein in chronic myelogenous leukemia). Using fluorescence-based and antigen-presentation assays, we determined that significant quantities of exogenously added peptide could accumulate in "designer" CRCL and could stimulate T cell activation. Further, we concluded that peptide-embedded CRCL, devoid of other antigens, could generate potent immunity against pre-established murine leukemia. Designer CRCL allows for the development of personalized vaccines against cancers expressing known antigens, by embedding antigens into CRCL derived from normal tissue.—Kislin, K. L., Marron, M. T., Li, G., Graner, M. W., Katsanis, E. Chaperone-rich cell lysate embedded with BCR-ABL peptide demonstrates enhanced anti-tumor activity against a murine BCR-ABL positive leukemia

Key Words: heat-shock proteins • peptide antigens • anticancer vaccine • T-cells • isoelectric focusing

This article has been cited by other articles:

				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]