Chaperone-rich cell lysate embedded with BCR-ABL peptide demonstrates enhanced anti-tumor activity against a murine BCR-ABL positive leukemia.
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
Kerri L
KL
Cancer Biology Interdisciplinary Program, University of Arizona, Tucson, Arizona, USA.
Marron
Marilyn T
MT
Li
Gang
G
Graner
Michael W
MW
Katsanis
Emmanuel
E
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D064032:Calbindin 2; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D004527:Egg Proteins / Q000276:immunology; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000008:administration & dosage / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*; D050884:HSP72 Heat-Shock Proteins / Q000008:administration & dosage / Q000032:analysis / Q000627:therapeutic use; D018841:HSP90 Heat-Shock Proteins / Q000008:administration & dosage / Q000032:analysis / Q000627:therapeutic use; D016233:Immunotherapy, Active; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy*; D008099:Liver / Q000737:chemistry*; D008562:Membrane Glycoproteins / Q000008:administration & dosage / Q000032:analysis / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018832:Molecular Chaperones / Q000008:administration & dosage / Q000032:analysis / Q000627:therapeutic use*; D009842:Oligopeptides / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments; D064030:S100 Calcium Binding Protein G / Q000008:administration & dosage / Q000032:analysis / Q000627:therapeutic use; D014020:Tissue Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*
D064032:Calbindin 2; D019496:Cancer Vaccines; D004527:Egg Proteins; D050884:HSP72 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; C110366:OVA-8; D009842:Oligopeptides; D010446:Peptide Fragments; D064030:S100 Calcium Binding Protein G; D014020:Tissue Extracts; C053387:endoplasmin; C521957:glycyl-phenylalanyl-lysyl-glutaminyl-seryl-seryl-lysyl-alanyl-leucine; D010047:Ovalbumin; D016044:Fusion Proteins, bcr-abl