PPHM at AACR (part 4 of 4 [for today])
Finally, the company says NOTHING about the other science presented today. Why?
The company seems so inept at summarizing studies.
There are other very, very serious issues about PPHM, regarding the mechanisms of action promoted for Bavituximab, the lack of interested biopharm partners and general lack of striking clinical data. But these issues can wait until after AACR. The company does not seem able, or perhaps willing to discuss in detail current status of the AACR studies as to updating their submission nearly 5 months ago.
In vivo binding of chTNT-1/B antibodies (Cotara) to DNA/histone complexes in tumors using near-infrared optical imaging
Jian Gong1, Roy Sevilla1, Vince Nguyen1, Seth Fisher1, Jessica Alldredge1, Jessie Kinjo1, Rich Archer1, Matthew Peacock2, Christopher Hughes2, Connie Chang1, Bruce Freimark1. 1Peregrine Pharmaceuticals, Inc., Tustin, CA; 2University of California, Irvine, Irvine, CA
Abstract Body: Tumors contain both microscopic and macroscopic areas of necrotic cells. These have abnormal cell membrane permeability, which allows passage of large macromolecules such as antibodies into the cell. 131I-chTNT-1/B antibody (Cotara) is a novel, single administration agent designed to target tumor necrosis that has completed a Phase II clinical trial for recurrent glioblastoma multiforme (GBM), showing 9.3 month median overall survival for patients. Since 131I-chTNT-1/B antibody is a high-molecular-mass protein, it cannot easily pass from the systemic circulation through the blood-brain barrier (BBB) and thus can only be delivered locally by an intratumoral catheter. We have developed a human ME-180 cervical carcinoma xenograft tumor model in nude mice to characterize the targeting of chTNT-1/B to necrotic areas using near infrared (NIR) optical imaging. The use of NIR optical imaging is a powerful translational tool to monitor in vivo antibody targeting. chTNT-1/B was labeled with a NIR fluorescent dye and kinetics of antibody retention in tumors was measured by NIR optical imaging following intratumoral injection of the NIR-chTNT-1/B. NIR-chTNT-1/B was retained in ME180 tumors for a longer duration compared to NIR dye alone. Labeling of chTNT-1/B with a low dye/protein ratio was necessary to demonstrate maximum specific targeting to tumor necrosis. Evaluation of in vivo antibody targeting to tumors using NIR imaging may facilitate improvements for treatment of patients with malignant glioma with Cotara. |
