Development of AGTII Prostate Cancer Therapeutic Lentivirus, AG1101

AGTII is targeting multiple pathways in cancer to develop more effective therapeutics. Examples of pathways being targeted are the p53 pathway, which is damaged in half of all cancers, and the BCL2 pathway, which is also dysfunctional in many cancers. Two AGTII lentivirus vectors, JZ2 and JZ3, target the p53 and the BCL2 pathways, respectively.

Analysis of the interaction of these two vectors in model systems is being used to guide development of AG1101. The data below show that AGTII's strategy identifies potent intervention combinations.

 

Treatment of prostate tumor xenografts

Tumor xenografts (PC3 cells) in thirty SCID mice were grown to approximately 40 mm³ (Control tumors) or 300 mm³ (AG1101 Treated tumors). On Day 1, vehicle containing JZ2, JZ3, or both was administered concurrently via intravenous and intratumoral injections; vehicle alone was administered to Controls. Additional doses were administered weekly. Tumors were measured in their longest dimension every week for 4 weeks.

 

Control	AG1101 Treated

 

As shown above, the Control tumors increased in size by over 2500%. In contrast, tumors treated with JZ2, JZ3, or both were reduced in size by approximately 95%. The residual tumor mass was dissected from each animal at the conclusion of the experiment. The average weight of the tumors from each group of mice was calculated and is shown below (left). The residual tumor tissue from each animal is shown below (right).

 

Examples of Control and AG1101 Treated tumors in their host animals are shown below.

Control	AG1101 Treated

The AG1101 Treated tumor has been reduced to a small mass of residual connective tissue.  In contrast, the Control tumor is large, well vascularized, and consists of healthy tissue.

In vivo expression of human prostate-specific antigen in AG1101 Treated versus Control tumors is shown below.

Control	AG1101 Treated

The Control tumor (left) expresses high levels of hPSA. In contrast, Expression of hPSA is completely eliminated in the residual tumor tissue from a tumor treated with AG1101 (right).