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, Emmanuel Katsanis

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2173-2184
Number of pages12
JournalFASEB Journal
Volume21
Issue number9
DOIs
StatePublished - Jul 2007

Keywords

  • Anticancer vaccine
  • Heat-shock proteins
  • Isoelectric focusing
  • Peptide antigens
  • T-cells

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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