The article detailed several exosomal mechanisms that promote cancer progression, including suppression of the immune system, triggering resistance to cancer therapies, promotion of angiogenesis and seeding the spread of metastasis. The article also indicated that high levels of circulating exosomes correlated with advanced stage cancer.
As researchers continue to unravel the deleterious mechanisms of exosomes underlying cancer, it has become clear that these particles also transport many molecular targets of interest to the pharmaceutical industry. Thus providing further support for a medical device that is able to target circulating exosomes without adding drug toxicity to established cancer therapies.
In this regard, I am pleased to share the following overview authored by Dr. Annette Marleau (our Director of Tumor Immunology), which outlines oncology targets of the pharmaceutical industry that have been reported to be transported by exosomes.
Therapeutic Elimination of Cancer Exosomes: Delivery Vehicles For A Spectrum of Pharmaceutical Industry Targets
The Aethlon Hemopurifier® is a first-in-class extracorporeal hemofiltration device with the ability to capture and retain disease-mediating particles from the entire circulatory system. Utilizing existing hemodialysis infrastructure, Hemopurifier® cartridges are packed with a carbohydrate-binding protein known as GNA, which has a unique affinity for glycosylated particles that are typically released in large quantities by diseased cells.
Among the disease targets that can be addressed by Hemopurifier® therapy are exosomes (also sometimes referred to as extracellular vesicles or microvesicles). Previously thought to represent unwanted cellular debris, an explosion of research has now proven that exosomes serve as primary transportation systems between the body's cells. In disease conditions such as cancer, pathogenic material from diseased cells is packaged into exosomes and released into circulation, thereby unleashing the cancer's arsenal of malignant signals throughout the body. In recent years, the scientific community has identified a complement of disease-causing proteins and genes carried in the exosomal cargo, the tumor's essential blueprint. Exosomes are thus major purveyors of aggressive cancer phenotypes, able to provide the comprehensive array of mediators for tumor growth and metastasis, drug resistance, immune suppression, and angiogenesis.
Drawing from the surplus of possible targets in cancer therapeutics, pharmaceutical companies are vying in a race for clinical enhancement and commercialization of a plethora of drug candidates, including tyrosine kinase inhibitors (TKI) and monoclonal antibodies (mAb) directed at specific mediators of malignancy. We envision that addressing exosomes therapeutically could serve as a strategy for dealing with many of these disease targets simultaneously. Indeed, an analysis of the drug targets being pursued by the pharmaceutical industry reveals that many of these targets are actually transported by cancer exosomes during the disease process. Included in the pipeline of promising oncology drugs are immune checkpoint inhibitors targeting programmed cell death protein 1 (also known as PD-1) and its ligand (PD-L1, B7-H1), a molecular pathway triggered by exosomes that contributes to muted anti-cancer responses. As underscored by the list that follows, the drug targets present in exosomes encompass the breadth of molecular pathways that are exploited by tumors to escape immune surveillance and hijack host tissues, including CTLA-4, HGF/met, FGF, b-Raf, EGFR, HER2, CD20, P-glycoprotein, and VEGF/VEGFR.
Programmed Cell Death 1 & Ligand (PD-1/PD-1L):
- Merck: Lambrolizumab/MK-3475 (anti-PD-1 mAb)
- Bristol-Myers Squibb: Nivolumab/BMS-936558 (anti-PD-1 mAb)
- CureTech/Teva: Pidilizumab/CT-011 (anti-PD-1 mAb)
- Roche/Genentech: MPDL3280A (anti-PD-L1 mAb)
- Medimmune/AstraZeneca: MEDI4736 (anti-PD-L1 mAb).
- Amplimmune/GlaxoSmithKline: AMP-224 (PD-L2-IgG1 Fc fusion protein).
- Bristol-Myers Squibb: Ipilimumab/Yervoy® (anti-CTLA-4 mAb)
- Medimmune/Pfizer: Tremelimumab/CP-675-206 (anti-CTLA-4 mAb)
Hepatocyte growth factor (HGF) & Receptor (Met):
- Amgen: Rilotumumab/AMG 102 (anti-HGF mAb)
- Genentech/Roche: Onartuzumab/OA-5D (anti-Met mAb)
- Aveo: Ficlatuzumab/AV-299 (anti-HGF mAb)
- Amgen: AMG 337 (MET TKI)
- Eli Lilly: LY-2875358 (anti-Met mAb).
- ArQule: Tivantinib/ARQ 197 (MET TKI)
- Novartis/Incyte: INCB28060/INC280 (MET TKI)
- Novarits: Dovitinib/TK1285 (FGFR, VEGFR & PDGF TKI)
- GlaxoSmithKline: Tafinlar™/Dabrafenib (B-raf kinase inhibitor)
- Genentech: Zelboraf®/Vemurafenib (B-raf kinase inhibitor)
- Genentech: Tarceva®/Erlotinib (EGFR TKI)
- Bristol-Myers Squibb & Eli Lilly: Cetuximab/Erbitux (anti-EGFR mAb)
- Amgen: Vectitbix/Panitumumab (anti-EGFR mAb)
- Boehringer Ingelheim: Gilotrif™/Afatinib (EGFR/HER2 TKI)
- Genentech: Herceptin®/Trastuzumab (anti-HER2 mAb)
- Genentech: Kadcyla®/Ado-trastuzumab emtansine (anti-HER2 mAb linked to DM1 drug)
- Genentech: Perjeta®/Pertuzimab (anti-HER2 mAb)
- GlaxoSmithKline: Tykerb/Lapatinib (dual TKI against HER2 and EGFR)
- Biogen Idec & Genentech: Rituxan®/Rituximab (anti-CD20 mAb)
- GlaxoSmithKline: Arzerra™/Ofatumumab (anti-CD20 mAb)
- Genentech: Gazyva™/Obinutuzumab (anti-CD20 mAb)
- Novartis: Valspodar/PSC-833 (P-glycoprotein inhibitor).
Vascular endothelial growth factor (VEGF) & Receptor (VEGFR):
- Genentech/Roche: Avastin®/Bevacizumab (anti-VEGF mAb)
- Eli Lilly: Cyramza™ /Ramucirumab (anti-VEGFR2 mAb)
- Exelixis/GlaxoSmithKline: Foretnib/XL880/GSK1363089 (MET/VEGFR2 inhibitor).
- Sanofi & Regeneron: Zaltrap®/Ziv-Afibercept (VEGFR1/2 IgG1 Fc fusion protein)
About Aethlon Medical, Inc.
Aethlon Medical creates innovative medical devices to address life-threatening diseases. The Aethlon ADAPT™ (Adaptive Dialysis-like Affinity Platform Technology) establishes the basis for a new class of therapeutics that target the rapid elimination of disease enabling particles from the circulatory system of treated patients. The lead Aethlon ADAPT™ product is the Hemopurifier®, a device that addresses a broad-spectrum of viral pathogens as well as tumorsecreted exosomes that suppress the immune system of cancer patients. Aethlon is also operating under two government contracts with the Defense Advanced Research Projects Agency (DARPA) related the development of a medical device to reduce the incidence of sepsis. Exosome Sciences, Inc. is a majority owned Aethlon subsidiary that is advancing exosome-based strategies to diagnose and monitor cancer and infectious disease progression. Additional information can be found at www.AethlonMedical.com
Certain statements herein may be forward-looking and involve risks and uncertainties. Such forward-looking statements involve assumptions, known and unknown risks, uncertainties and other factors which may cause the actual results, performance or achievements of Aethlon Medical, Inc. to be materially different from any future results, performance, or achievements expressed or implied by the forward-looking statements. Such potential risks and uncertainties include, without limitation, that the ESI will not be able to commercialize its future products, that the FDA will not approve the initiation of the Company's existing or future clinical programs or provide market clearance of the company's products, future human studies whether revenue or non-revenue generating of the Aethlon ADAPT™ system or the Aethlon Hemopurifier® as an adjunct therapy to improve patient responsiveness to established cancer or hepatitis C therapies or as a standalone cancer or hepatitis C therapy, the Company's ability to raise capital when needed, the Company's ability to complete the development of its planned products, the Company's ability to manufacture its products either internally or through outside companies and provide its services, the impact of government regulations, patent protection on the Company's proprietary technology, the ability of the Company to meet the milestones contemplated in the DARPA contract, product liability exposure, uncertainty of market acceptance, competition, technological change, and other risk factors. In such instances, actual results could differ materially as a result of a variety of factors, including the risks associated with the effect of changing economic conditions and other risk factors detailed in the Company's Securities and Exchange Commission filings. The Company undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise.
James A. Joyce
Chairman and CEO
Chief Financial Officer
Published at Investorideas.com newswire
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