title: Tumor-derived chaperone-rich cell lysates are effective therapeutic vaccines against a variety of cancers.
abstract: With the clinical use of purified, tumor-derived chaperone proteins as anti-cancer vaccines already in clinical trial stages, we have focused our attention on the utility of chaperone-rich cell lysates (CRCL) in cancer immunotherapy. CRCL, as prepared from tumor lysates via a free solution-isoelectric focusing (FS-IEF) technique, is a high-yield vaccine enriched for numerous chaperone proteins. We have compared the efficacy of CRCL vaccines to that of individual chaperone protein vaccines in in vivo settings, including ELISPOT assays, tumor-growth assays and survival assays. In all experiments, CRCL vaccines were at least as effective, and in some settings perhaps even more effective, than either of the two most heavily studied components of CRCL, HSP70 and GRP94/gp96, in reduction in tumor growth and prolongation of survival in both prophylactic and pre-existing tumor settings against tumors of diverse origin and genetic background. Combining CRCL preparations with dendritic cells ex vivo resulted in a cellular vaccine that could eradicate pre-existing tumors in a high percentage of cases. The high yields of CRCL vaccines from small quantities of starting materials, the relative ease of its procurement and the functional data presented here suggest that CRCL vaccines are worthy of evaluation in pilot clinical trial cancer immunotherapy protocols.
authors.affiliation: Department of Pediatrics, Steele Memorial Children's Research Center, University of Arizona, 1501 North Campbell Ave., P.O. Box 245073, Tucson, AZ 85724, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Graner
authors.forename: Yi
authors.initials: Y
authors.lastname: Zeng
authors.forename: Hanping
authors.initials: H
authors.lastname: Feng
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Katsanis
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000627:therapeutic use; D002455:Cell Division; D002457:Cell Extracts / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000637:transplantation; D006360:Heat-Shock Proteins / Q000276:immunology* / Q000302:isolation & purification; D007371:Interferon-gamma / Q000096:biosynthesis; D007525:Isoelectric Focusing; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018832:Molecular Chaperones / Q000276:immunology* / Q000302:isolation & purification; D009374:Neoplasms, Experimental / Q000737:chemistry / Q000517:prevention & control / Q000628:therapy*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D019496:Cancer Vaccines; D002457:Cell Extracts; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D007371:Interferon-gamma