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 2 Correspondence: 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@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
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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
Kislin, Kerri L.; Marron, Marilyn T.; Li, Gang; Graner, Michael W.; Katsanis, Emmanuel
Follow The FASEB Journal
, Volume 21 (9): 2173
Fed of American Socs for Experimental Biology – Jul 1, 2007
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