TY - JOUR
T1 - Tumor-derived multiple chaperone enrichment by free-solution isoelectric focusing yields potent antitumor vaccines
AU - Graner, Michael
AU - Raymond, Amy
AU - Akporiaye, Emmanuel
AU - Katsanis, Emmanuel
N1 - Funding Information:
Acknowledgements The authors wish to thank Payal Patel, Susan Hoy, Hector Sandoval, and Denise Kent for superb technical help. This work was supported in part by Arizona Disease Control Research Commission, the Leukemia and Lymphoma Society of America, the W.M. Keck Foundation, the Enid and Mel Zucker-man Fund, the Michael Landon Fund and the Arizona Elk s Program in Transplantation Research.
PY - 2000
Y1 - 2000
N2 - We have utilized a free-solution/isoelectric focusing technique (FS-IEF) to obtain fractions rich in multiple chaperone proteins from clarified A20 tumor lysates. Vaccines prepared from chaperone-rich fractions are capable of providing protective immunity in mice subsequently challenged intravenously with the same A20 B cell leukemia cells. This protection is at least equal to that provided by purified, tumor-derived heat-shock protein 70, which was the best chaperone immunogen in our hands against this aggressive murine leukemia model. Dosage escalation studies, however, revealed that increasing vaccine dosages actually abrogated the protective effects. The physical nature of the enriched chaperones indicates that they are associated in complexes, which may have implications for their function, FS-IEF is relatively simple, rapid, and efficient, thus making combined multi-chaperone therapy feasible.
AB - We have utilized a free-solution/isoelectric focusing technique (FS-IEF) to obtain fractions rich in multiple chaperone proteins from clarified A20 tumor lysates. Vaccines prepared from chaperone-rich fractions are capable of providing protective immunity in mice subsequently challenged intravenously with the same A20 B cell leukemia cells. This protection is at least equal to that provided by purified, tumor-derived heat-shock protein 70, which was the best chaperone immunogen in our hands against this aggressive murine leukemia model. Dosage escalation studies, however, revealed that increasing vaccine dosages actually abrogated the protective effects. The physical nature of the enriched chaperones indicates that they are associated in complexes, which may have implications for their function, FS-IEF is relatively simple, rapid, and efficient, thus making combined multi-chaperone therapy feasible.
KW - Antitumor immunity
KW - Chaperones
KW - Complexes
KW - Isoelectric focusing
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U2 - 10.1007/s002620000138
DO - 10.1007/s002620000138
M3 - Article
C2 - 11092614
AN - SCOPUS:0033762022
SN - 0340-7004
VL - 49
SP - 476
EP - 484
JO - Cancer Immunology Immunotherapy
JF - Cancer Immunology Immunotherapy
IS - 9
ER -