Tuesday, March 10, 2009

Anthrax Toxin-Mediated Delivery In Vivo and In Vitro of a Cytotoxic T-Lymphocyte Epitope from Ovalbumin

The field of immunotherapy is a growing area where the use of synthetic peptides can be very helpful. As we all know Anthrax has received a lot of attention for its potential to be a low cost potential biochemical warfare agent. In this article the researchers describe how a non-toxic strain of anthrax toxin is able to deliver a cytotoxic T-lymphocyte (CTL) epitope in vivo, so that a unique CTL response is primed against the epitope.
This bacterial origin epitope, was then fused to the amino-terminal fragment (LFn) from the lethal-factor component of the toxin, and this chimeric protein was then injected, along with the protective antigen (PA) portion , into BALB/c mice. The authors then describe that indeed this fusion protein ( PA plus LFn) is able to deliver a different epitope, for example OVA257–264 from ovalbumin. Delivery was carried out in a different mouse haplotype, H-2Kb and took place in vitro as well as in vivo. An specific CTL clone, OVA257-264GA-4, was shown to recognize EL-4 cells treated in vitro with PA containing as little as 30 fmol of the LFn-OVA257–264 fusion protein. Also, OVA257–264-specific CTL can proliferate by incubation with splenocytes reacted with PA plus LFn-OVA257–264. In summary this work shows the potential for PA-LFn to serve as a universal delivery vehicle for CTL epitopes in vivo and also as a safe tool for the in-vitro expansion of patient-derived CTL for applications in adoptive immunotherapy.

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