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Granulocyte-macrophage colony-stimulating factor: an effective adjuvant for
protein and peptide-based vaccines
ML Disis, H Bernhard, FM Shiota, SL Hand, JR Gralow, ES Huseby, S Gillis and MA Cheever
Department of Medicine, University of Washington, Seattle 98195-6227, USA.
The current studies evaluate granulocyte-macrophage colony-stimulating
factor (GM-CSF) as a vaccine adjuvant. An important issue for developing
vaccine therapy for human malignancy is identifying adjuvants that can
elicit T-cell responses to proteins and peptides derived from "self" tumor
antigens. GM-CSF, in vitro, stimulates the growth of antigen-presenting
cells such as dendritic cells and macrophages. Initial experiments examined
whether GM-CSF injected into the skin of rats could affect the number or
character of antigen presenting cells, measured as class II major
histocompatability complex expressing cells, in lymph nodes draining the
injection site. Intradermal (id) inoculation of GM-CSF every 24 hours for a
total of five inoculations resulted in an increase of class II+ fluorescing
cells that peaked at the fourth inoculation. Subcutaneous (sq) inoculation
resulted in an increase of class II+ fluorescing cells that peaked
following the second inoculation, then decreased over time. Using this
schema for "conditioning" the inoculation site, GM-CSF was administered id
or sq for five injections and a foreign antigen, tetanus toxoid (tt), was
given at the beginning or the end of the immunization cycle. Id
immunization was more effective than sq at eliciting tt specific immunity.
In addition, GM-CSF id, administered as a single dose with antigen,
compared favorably with complete Freund's adjuvant (CFA) and alum in
eliciting tt specific antibody and cellular immunity. We have shown that
immunity to rat neu (c-erbB-2) protein, an oncogenic self protein, can be
generated in rats by immunization with peptides derived from the normal rat
neu sequence plus CFA. The current study demonstrates that rat neu peptides
inoculated with GM-CSF could elicit a strong delayed type hypersensitivity
reaction (DTH) response, whereas peptides alone were non-immunogenic.
GM-CSF was as effective as CFA in generating rat neu specific DTH responses
after immunization with a neu peptide based vaccine. Soluble GM-CSF is a
potent adjuvant for the generation of immune responses to foreign proteins
as well as peptides derived from a self tumor antigen.
Volume 88,
Issue 1,
pp. 202-210,
07/01/1996
Copyright © 1996 by The American Society of Hematology
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S. Siena, M. Di Nicola, R. Mortarini, A. Anichini, M. Bregni, G. Parmiani, and A. M. Gianni
Expansion of Immunostimulatory Dendritic Cells from Peripheral Blood of Patients with Cancer
Oncologist,
February 1, 1997;
2(1):
65 - 69.
[Full Text]
[PDF]
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