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Infect Immun, February 1998, p. 615-619, Vol. 66, No. 2
Department of Microbiology and Molecular
Genetics, Harvard Medical School, Boston, Massachusetts 02115
Received 14 August 1997/Returned for modification 15 October
1997/Accepted 20 November 1997
We reported earlier that a nontoxic form of anthrax toxin was
capable of delivering a cytotoxic T-lymphocyte (CTL) epitope in vivo,
such that a specific CTL response was primed against the epitope. The
epitope, of bacterial origin, was fused to an N-terminal fragment (LFn)
from the lethal-factor component of the toxin, and the fusion protein
was injected, together with the protective antigen (PA) component, into
BALB/c mice. Here we report that PA plus LFn is capable of
delivering a different epitope
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Anthrax Toxin-Mediated Delivery In Vivo and In
Vitro of a Cytotoxic T-Lymphocyte Epitope from Ovalbumin
OVA257-264 from ovalbumin.
Delivery was accomplished in a different mouse haplotype,
H-2Kb and occurred in vitro as well as in vivo.
An OVA257-264-specific CTL clone, GA-4, recognized EL-4
cells treated in vitro with PA plus as little as 30 fmol of the
LFn-OVA257-264 fusion protein. PA mutants attenuated in
toxin self-assembly or translocation were inactive, implying that the
role of PA in epitope delivery is the same as that in toxin action.
Also, we showed that OVA257-264-specific CTL could be
induced to proliferate by incubation with splenocytes treated with PA
plus LFn-OVA257-264. These findings imply that PA-LFn may
serve as a general delivery vehicle for CTL epitopes in vivo and as a
safe, efficient tool for the ex vivo expansion of patient-derived CTL
for use in adoptive immunotherapy.
*
Corresponding author. Mailing address: Department of
Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Ave., Boston, MA 02115. Phone: (617) 632-1873. Fax: (617)
738-7664. E-mail: mstarnba{at}warren.med.harvard.edu.
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