Tumor-derived multiple chaperone enrichment by free-solution isoelectric focusing yields potent antitumor vaccines |
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Authors: | Michael Graner Amy Raymond Emmanuel Akporiaye Emmanuel Katsanis |
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Institution: | (1) Department of Pediatrics, Steele Memorial Children's Research Center, University of Arizona, 1501 N. Campbell Ave, P.O. Box 245073, Tucson, Arizona 85724-5073, USA e-mail: katsanis@peds.arizona.edu Tel.: +1-520-626-6527; Fax: +1-520-626-4220, US;(2) Department of Microbiology and Immunology, University of Arizona, P.O. Box 245049, Tucson, Arizona 85724-5049, USA, US |
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Abstract: | 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.
Received: 11 May 2000 / Accepted: 13 June 2000 |
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Keywords: | Isoelectric focusing Chaperones Complexes Antitumor immunity |
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