Intra-Prostate Cancer Vaccine Inducer
Final rept. 26 Jan 2004-25 Jan 2007
ANTIGEN EXPRESS INC WORCESTER MA
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Antigen Express has generated potent human Ii-RNAi constructs for use in prostate cancer therapy. We identified active Ii- RNAi sequences, selected the most active promoter CMV and demonstrated good suppression of Ii. The constructs also were used to enhance a gp120 DNA vaccine model, confirming that Ii suppression increases the potency of a tumor cell and DNA vaccine. We have shown that an anti-tumor immune response can be strongly induced by intratumoral induction of the MHC class 11111- phenotype and effectively and specifically protects mice from re-challenge by the same tumor cells. The frequency and dose of plasmid injections have been optimized as well as the dose of IL-2 to induce a potent immune response following generation of the MHC class 11111- phenotype. The duration of plasmid in cells in vitro and the in vivo have been evaluated and indicate that this immunotherapy should be safe. Finally, we have found that DU-145, PC-3, and LNcap prostate cell lines are heterogeneous for MHC class 11 and 11 expression and that PC-3 and LNcap cells are MHC class II-Ii. Overall, our results suggest that Ii suppression has the potential to be an elegant method for prostate cancer immunotherapy.
- Medicine and Medical Research