Immunoprotective activities of multiple chaperone proteins isolated from murine B-cell leukemia/lymphoma.
Although the use of tumor-derived heat shock/chaperone proteins (HSPs) as anticancer vaccines is gaining wider study and acceptance, there have thus far been no reports concerning chaperone antitumor activities against disseminated hematological malignancies. We have devised an efficient and effective method for purification of the chaperone proteins grp94/gp96, HSP90, HSP70, and calreticulin from harvested A20 murine leukemia/lymphoma tumor material. We have demonstrated that these purified proteins, when used as vaccines, can induce potent and specific immunity against a lethal tumor challenge. Individual chaperone proteins were differentially effective in their abilities to provide immune protection. The increase in survival generated by the most effective chaperone vaccine, HSP70, resulted from at least a 2-log reduction in tumor burden. Syngeneic granulocyte macrophage colony-stimulating factor producing fibroblasts were injected at the site of vaccination in an attempt to augment the immune response. Surprisingly, localized granulocyte macrophage colony-stimulating factor production inhibited the protective effects of chaperone vaccination. These studies provide evidence that chaperone proteins can be isolated from B-cell tumors and used effectively to immunize against disseminated lymphoid malignancies.
Graner
M
M
Department of Pediatrics, Steele Memorial Children's Research Center, University of Arizona, Tucson 85724-5073, USA.
Raymond
A
A
Romney
D
D
He
L
L
Whitesell
L
L
Katsanis
E
E
D016475:3T3 Cells; D000818:Animals; D002135:Calcium-Binding Proteins / Q000302:isolation & purification / Q000627:therapeutic use; D037282:Calreticulin; D019496:Cancer Vaccines / Q000302:isolation & purification / Q000627:therapeutic use; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000302:isolation & purification / Q000627:therapeutic use; D018841:HSP90 Heat-Shock Proteins / Q000302:isolation & purification / Q000627:therapeutic use; D007109:Immunity; D007114:Immunization; D015448:Leukemia, B-Cell / Q000276:immunology / Q000517:prevention & control*; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000517:prevention & control*; D008565:Membrane Proteins / Q000302:isolation & purification / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D018832:Molecular Chaperones / Q000302:isolation & purification / Q000627:therapeutic use*; D012261:Ribonucleoproteins / Q000302:isolation & purification / Q000627:therapeutic use; D016019:Survival Analysis; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
D002135:Calcium-Binding Proteins; D037282:Calreticulin; D019496:Cancer Vaccines; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D012261:Ribonucleoproteins; C018551:glucose-regulated proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor