(Nanowerk News) Abraxis BioScience Inc. today announced that multiple studies showcasing its proprietary tumor targeting technology, known as the nab® (nanoparticle albumin-bound) technology platform, and secreted protein acidic and rich in cysteine (SPARC) biomarker will be presented at the American Association for Cancer Research (AACR) Annual Meeting in Denver, April 18-22, 2009. Abraxis BioScience will have a significant presence at this year’s AACR meeting, presenting a total of 10 abstracts, including one oral presentation on preclinical studies for the company’s leading product, ABRAXANE® for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound), the biomarker SPARC and its development pipeline, including:
ABRAXANE (Nab-Paclitaxel) and SPARC
Poster 1478: Mechanisms of Nab-Paclitaxel and Anti-VEGF Combination Therapy in the Inhibition of Breast Tumor Survival and Inflammatory Response
Poster 2572: Detection of SPARC with mRNA with Q3 Deletion in Clinical Samples
Poster 3769: Nab-Paclitaxel Results in Reduced Therapy-Related Fatigue in Mice as Compared to Cermophor-based Paclitaxel
Poster 4017: Identification of the albumin binding domain and the angiogenic domain of SPARC
Poster 5168: DNMT3a Mediates Promoter Hypermethylation of SPARC in Ovarian Cancer
Abraxis BioScience Pipeline
Poster 136: CNS Safety, Antitumor Activity, and Anti-Angiogenic Activity of Nab-Rapamycin (ABI-009)
Poster 4576: Potent Anti-tumor Effects of Nab-Rapamycin (ABI-009) in Combination with Kinase Inhibitors Erlotinib and Perifosine
Poster 2927: Pharmacokinetic and Cardiovascular Safety Profile of ABI-011 in Cynomolgus Monkeys
Poster 5571: Vascular Disrupting Activity of ABI-011
Oral Presentation 5638: Sequence-dependent enhancement of antitumor activity of the vascular disrupting agent ABI-011 by Nab-Paclitaxel and Bevacizumab
Highlights From Poster No. 4017, Desai: Identification of the albumin binding domain and the angiogenic domain of SPARC
One important study being presented examines the relationship between a tumor biomarker, SPARC, and tumor blood vessel growth and metastasis, also referred to as angiogenesis (Poster No. 4017, Desai: Identification of the albumin binding domain and the angiogenic domain of SPARC). These findings reinforce the role of Abraxis’ novel chemotherapy agent ABRAXANE in increased anti-angiogenic and anti-tumor activity due to the unique albumin-bound delivery mechanism provided through the nab® technology platform.
“Preliminary clinical studies have suggested a direct correlation between elevated levels of SPARC and positive response to ABRAXANE,” said Patrick Soon-Shiong, M.D., chairman and chief executive officer of Abraxis BioScience. “These new data improve our understanding of SPARC and further confirm the benefits of albumin-bound nab technology in enhancing delivery of chemotherapy.”
The data support ABRAXANE’s unique nab® technology, which exploits tumor biology to deliver more effective and targeted chemotherapy treatment. In normal tumor biology, SPARC secreted by the tumor would be used to recruit nutrients carried by naturally occurring albumin. This research further reinforces that with ABRAXANE’s nab® technology, SPARC binds to the albumin-bound medicine; instead of delivering nutrients to the tumor, it delivers chemotherapy, killing cancer cells and halting tumor growth.
The study was designed to define the role of SPARC in fostering blood vessel growth and tumor invasiveness and characterize the protein’s angiogenic and albumin binding-domains – the lock and key formations that allow albumin to bind to the SPARC protein.
Using recombinant human SPARC (rhSPARC) grown in vitro, researchers determined that rhSPARC fostered the growth of new blood vessels (pro-angiogenesis) at physiological levels of SPARC found in cancer tumors.
The addition of rhSPARC also resulted in the development of more mature blood vessels well-supported by pericytes (smaller, supporting blood vessels wrapped around capillaries), suggesting that SPARC plays a greater role in the angiogenic process beyond initiating the growth of new blood vessels.
Researchers determined that the protein’s angiogenic domain was located on the carboxyl, or C-terminus, of the SPARC molecule.
The albumin binding domain was found to be localized to amino acids 209-223 of the SPARC molecule.
rhSPARC and albumin were found to bind sustainably at levels similar to the plasma concentration of albumin in the body.
“Abraxis’ research on SPARC is part of our ongoing commitment to pursue scientific models that support giving the right treatment to the right patient at the right time,” said Neil Desai, PhD, Senior Vice President, Global Research and Development. “This research further confirms that our nab technology platform provides a novel approach to cancer treatment through a unique delivery mechanism.”
Additional data presented at the meeting included combination studies of the pipeline drugs ABI-009 (nab-rapamycin) and the vascular disruptive agent ABI-011 (nab-5404). ABI-009 is a signal transduction inhibitor that targets the mTOR pathway, which is critical to cell proliferation and survival. ABI-011 is an investigational agent designed to directly disrupt tumor vasculature to compromise tumor growth and progression. Both agents utilize Abraxis’ proprietary nab delivery mechanism and are currently being studied for a wide range of solid tumor types.