The PNP Technology
Key Studies
To date, PNP scientists have conducted over 400 individual studies in various animal models documenting the performance characteristics and validity of PNP's therapeutic approach. Most prominent amongst these are studies demonstrating therapeutic efficacy and the fact that only a small percentage of the total volume of tumor cells need be transfected to achieve significant reductions in tumor volume; the so-called "bystander effect".
Bystander effect: In the experiment shown below, mice bearing D54 flank tumors in which 2.5%, 5%, or 10% of the tumor cells express E. coli PNP were treated with F-araAMP. F-araAMP is not effective against D54 tumors that do not express E. coli PNP (data not shown). Three days of treatment with F-araAMP resulted in excellent activity against D54 tumors in which as few as 2.5 % of the cells expressed E. coli PNP, and F-araAMP was able to cure mice of tumors in which 10% of the cells expressed E. coli PNP. These results indicate that excellent activity can be obtained with F-araAMP even when a small fraction of the tumor cells express E. coli PNP.
Demonstrated efficacy: The image below shows representative mice from an experiment to determine the effect of the PNP Therapeutic Strategy on the growth of tumors expressing E. coli PNP coupled with an early-generation prodrug, MeP-dR.
Mouse #1 bears a transplanted human (D54) tumor that has not been transfected with E. coli PNP nor was it treated with MeP-dR.
Mouse #2 bears a transplanted human (D54) tumor that has not been transfected with E. coli PNP but this animal has been treated with MeP-dR.
Mouse #3 bears a transplanted human (D54) tumor that does express the E. coli PNP gene but the animal has not been treated with the prodrug MeP-dR.
Mouse #4 bears a transplanted human (D54) tumor that expresses E. coli PNP and this animal was also treated with the pro-drug MeP-dR.