SAN DIEGO, Jan. 15, 2013 /PRNewswire/ -- Aethlon Medical, Inc. (OTCBB: AEMD), today released the following note authored by its Chairman and CEO, Jim Joyce.
In 2012, researchers published the discovery that small particles known as exosomes are secreted by tumors to seed the creation and spread of cancer metastases. These same tumor-secreted exosomes have also been implicated in death of immune cells necessary to combat cancer and they facilitate the ability of tumors to create their own blood supply for survival. The Aethlon Hemopurifier® is the first therapeutic strategy to address these vital targets in cancer care. Based on our early research in the field, we have issued patent protection that provides an opportunity to establish a dominant position within the marketplace. In this regard, we envision the elimination of tumor-secreted exosomes through Hemopurifier® therapy will optimize the performance of cancer therapies and augment the immune system's ability to combat cancer. Based on evidence that our Hemopurifier® captures exosomes underlying breast cancer, I am pleased to provide you with the following review authored by Dr. Annette Marleau, our Director of Tumor Immunology.
Current Perspectives on Breast Cancer Exosomes
Breast cancer represents a challenging clinical scenario that exhibits heterogeneous molecular types and enormous diversity of malignant behavior of tumors between patients. As the second most common cancer afflicting women in the United States, it is estimated that 1 in 8 women will be diagnosed with invasive breast cancer in their lifetime (1). Significant improvements in disease-free survival have been achieved; however, there is still a need to address the aggressive and metastatic forms of breast cancer.
Advances in the understanding of breast cancer pathogenesis at a molecular level have pointed toward central roles for exosomes, nano-vesicles released in abundance by cancer cells. Exosomes are packed with proteins and genetic material from the tumor, and act as cellular messengers that distribute these malignant factors systemically to target cells, including cancer cells as well as healthy cells. Recently, the dissemination of pro-cancer cargo by exosomes is has been appreciated as promoting several critical aspects of cancer pathogenesis, including signaling for tumor growth, metastasis, angiogenesis, and resistance to chemo- and immunotherapeutic agents. These scientific discoveries, some of which are discussed below, have been accompanied by a growing interest in means for targeting exosomes therapeutically.
Recent studies have identified several mechanisms underlying the secretion of breast cancer exosomes and their uptake by target cells. In the breast tumor microenvironment, hypoxia is a pathological state of oxygen deprivation that affects the expression of genes required for many critical aspects of cancer progression. A study by Dr. Jonathan Gleadle's laboratory in the journal BMC Cancer demonstrated that hypoxia stimulates exosome secretion by breast cancer cells (2), which can serve as a means for distributing a supply of cancer-promoting signals for the tumor mass. These investigations and many others also point toward exosomes as biomarkers for predicting the aggressiveness of a tumor.
Adding to the understanding of the physiological triggers of exosome secretion, Dr. Josiah Ochieng's group reported in PLoS One that exosomes are secreted in response to detachment of breast cancer cells from extracellular matrices (3). In turn, the secreted exosomes concentrate on the surfaces of breast cancer cells to facilitate their re-adhesion to surfaces. This study implicates cancer-secreted exosomes as having crucial roles in tissue invasion by metastasizing breast cancer cells. Aberrant glycosylation is a hallmark of cancer that promotes adhesiveness of cancer cells to one another and to extracellular matrices, endowing them with invasive and metastatic phenotypes. Indeed, tumor-secreted exosomes also display highly glycosylated surface structures (4), which could serve as binding targets of lectin affinity capture agents for pulling nanovesicles out of the circulatory system.
Recent studies have also provided considerable insight into the impact of breast cancer exosomes as vehicles for spreading oncogenic signals to diverse target cells. A pivotal publication in PNAS by Dr. Richard Cerione's group at Cornell University showed that the transfer of cargo by cancer exosomes is involved in cellular transformation, whereby healthy cells acquired the growth characteristics of tumor cells (5). Along these same lines is the recent publication in PLoS One, authored by Drs. Chang Lau and David Wong at UCLA, where breast cancer exosomes interacted with salivary gland cells, as evidenced by changes in the protein and genetic composition of exosomes secreted by the target cells(6). This report provides mechanistic insight as to how tumors are capable of communicating with target cells at distant sites via secretion of exosomes, making a therapeutic strategy for systemic removal of exosomes an attractive possibility for slowing cancer progression.
Significantly, there is also evidence that breast cancer exosomes might exert a direct role in resistance of tumors to therapeutic agents. In a paper by Dr. Serenella Pupa and colleagues published in the Journal of Cellular Physiology, exosomes from breast cancer cells that over-expressed the HER2 oncoprotein also displayed surface HER2, which bound to and sequestered the therapeutic antibody Herceptin in vitro (7). It was suggested that this decoy effect of cancer exosomes could lower the therapeutic benefits of immunotherapeutic agents, particularly in patients with advanced cancer where the exosome burden is expected to be high. On this basis, a strategy aimed at alleviating the exosome load might prove to be a promising adjunct therapy to improve the benefits of standard of care breast cancer treatments.
King HW, Michael MZ and Gleadle JM. Hypoxic enhancement of exosome release by breast cancer cells. BMC Cancer 2012; 12:421.
Koumangoye RB, Sakwe AM, Goodwin JS, Patel T, Ocheing J. Detachment of breast tumor cells induces rapid secretion of exosomes which subsequently mediate cellular adhesion and spreading. PLoS One 2011; 6(9)e24234.
Batista BS, Eng WS, Pilobello KT, Hendricks-Munoz KD, Mahal LK. Identification of a conserved glycan signature for microvesicles.J Proteome Res. 2011 Oct 7;10(10): 4624-33.
Antonyak MA, Li B, Boroughs LK, Johnson JL, Druso JE, Bryant KL, Holowka DA, Cerione RA. Cancer cell-derived microvesicles induce transformation by transferring tissue transglutaminase and fibronectin to recipient cells. ProcNatlAcadSci U S A. 2011 Mar 22; 108(12):4852-7.
Lau CS, Wong DT. Breast cancer exosome-like microvesicles and salivary gland cells interplay alters salivary gland cell-derived exosome-like microvesicles in vitro. PLoS One. 2012; 7(3):e33037.
Ciravolo V, Huber V, Ghedini GC, Venturelli E, Bianchi F, Campiglio M, Morelli D, Villa A, Della Mina P, Menard S, Filipazzi P, Rivoltini L, Tagliabue E, Pupa SM. Potential role of HER2-overexpressing exosomes in countering trastuzumab-based therapy. J Cell Physiol. 2012 Feb; 227(2):658-67.
About Aethlon Medical
Aethlon Medical creates innovative medical devices that address unmet medical needs in cancer, infectious disease, and other life-threatening conditions. Our Aethlon ADAPT System is a revenue-stage technology platform that provides the basis for a new class of devices the rapid, yet selective removal of disease promoting particles from the entire circulatory system. At present, The Aethlon ADAPT product pipeline includes the Aethlon Hemopurifier® to address infectious disease and cancer, and a medical device being developed under a 5-year contract with Defense Advanced Research Projects Agency (DARPA) to reduce the incidence of sepsis in combat-injured soldiers. For more information, please visit www.aethlonmedical.com.
About The Aethlon Hemopurifier®
The Aethlon Hemopurifier® is a first-in-class medical device that selectively targets the rapid clearance of infectious viral pathogens and immunosuppressive proteins from the entire circulatory system. In the treatment of Hepatitis C virus (HCV), human studies have demonstrated that Hemopurifier® therapy may improve immediate, rapid and sustained virologic response rates when administered in the first few days of standard-of-care drug therapy. In addition to accelerating viral load depletion, post-treatment analysis of the Hemopurifier® has documented the capture of up to 300 billion HCV copies of HCV during a single six-hour treatment. Access to Hemopurifier® therapy is available on a compassionate-use basis through the Medanta Medicity Institute (Medicity), a leading center for medical tourism in India. The Medicity is offering treatment access to infected individuals who previously failed or subsequently relapsed standard-of-care drug regimens. The Hemopurifier® is also being offered as a salvage therapy to infected individuals who suffer a viral breakthrough during standard-of-care therapy. U.S. studies of the Hemopurifier® are currently pending approval of an IDE submitted to FDA.
The Aethlon Hemopurifier® and Cancer
In addition to the opportunity to address a broad-spectrum of infectious viral pathogens, the Hemopurifier® has been discovered to capture tumor-derived exosomes underlying several forms of cancer. Tumor-derived exosomes have recently emerged to be a vital therapeutic target in cancer care. These microvesicular particles suppress the immune response in cancer patients through apoptosis of immune cells and their quantity in circulation correlates directly with disease progression. Beyond possessing immunosuppressive properties, tumor-derived exosomes facilitate tumor growth, metastasis, and the development of drug resistance. By addressing this unmet medical need, the Hemopurifier® is positioned as an adjunct to improve established cancer treatment regimens.
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 FDA will not approve the initiation of the Company's clinical programs or provide market clearance of the company's products, future human studies whether revenue or non-revenue generating from either compassionate use or non-compassionate use 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, 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
SOURCE Aethlon Medical, Inc.