The Use of Venezuelan Equine Encephalitis Replicons Encoding the Her-2/neu Tumor Associated Antigen for the Prevention and Treatment of Breast Cancer
Annual rept. 15 Apr 2000-14 Apr 2001
NORTH CAROLINA UNIV AT CHAPEL HILL
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Much of the work described for Specific Aim 1 has now been completed. We have finished the in vitro testing and packaging of the replicon constructs described, and have begun work on additional constructs. Progress has been made characterizing the CD8 T cell response in both wild type and Her-2neu transgenic mice with generation of consistent CTL activity in the wild type mice. Additionally, we have cloned overlapping fragments of the Her-2neu gene into a bacterial expression system, and demonstrated a proliferative response to one of the recombinant proteins. These fragments will be used to evaluate CD4 T helper responses in immunized mice. We believe an immunotherapeutic protocol consisting of the appropriate combination and antigen and cytokine encoding repticons will be useful for overcoming the tolerance associated with the Her-2neu transgenic mice. In our initial tumor challenge experiment with replicons encoding Mer-2neu alone, we failed to mediate rejection of transferred Neu expressing tumors in Her-2neu transgenic mice. Again, we feel it will be a matter of determining the appropriate cytokine encoding constructs for use in our protocol.
- Medicine and Medical Research