Aethlon Medical (AEMD) Note: An Emerging Strategy to Treat Metastatic Breast Cancer
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.
The removal of exosomes by the HP in cancer treatment is a huge plus for AEMD. AEMD has a patent on the technology and it looks as if many cancer researchers/studies are focusing more and more on the removal of exosomes in the treatment of many cancers especially advanced stage. It would seem the FDA would be falling all over themselves to give AEMD a waiver in order to get the HP in use if nothing else as a compassionate device and start saving lives that are otherwise lost in most cases.
The safety of the HP has been proven over and over with the extensive studying of it's use in HCV treatment and several cancer studies from what I have gathered also. If the safety has been proven what does the FDA have to lose by approving it's use in otherwise basically hopeless cases? That is unless 'Big Pharma' is using their dollars and influence to hold back the technology since the HP could cut into their sales of cancer treatment Meds by increasing treatment efficacy which may reduce the need for as much medication in treatment. Less Med=less dollars in 'Big Pharma's' pockets.
My wife used to be a 'Big Pharma' Rep. and I was brainwashed, as she was into thinking they only wanted what is best for the public, as the FDA should be too. I question that now after seeing the FDA turn away treatments that do not benefit 'Big Pharma' but smaller companies that have refused to sell or promote in concert with the large companies.
AEMD is on the verge of breaking through and once we get the approval by the FDA to start testing here in the USA or possibly compassionate treatment for HCV, Cancer or both this company will make us some big money. I have backed away from many of the medical pennies that I used to recklessly invest in seeing great potential but always something being heartbreaking or a company releasing false Info that killed the opportunity if there actually was one. I have stuck with AEMD because I truly believe in the HP and believe it will pay off if we don't somehow get beat to the punch with a better treatment regimen, either pharmaceutically, a medical device or a combination of both.
I truly believe our future is drawing very near!!!
Just to possibly correct one thing you stated, about the HP's safety having been proven in "...several cancer studies..." I don't think that the HP has actually been used on live patients, rather that blood has been drawn from these patients and then run through the HP. To the best of my knowledge, at least in the U.S., using the HP on live humans has not yet been approved. I am hopeful that the current IDE at the FDA will allow AEMD to proceed with the 10-patient study on the HCV-affected end-stage renal patients, and that the reviews of those procedures will then allow the HP to be used for other applications, such as hoped for testing on cancer patients, at some center such as M.D. Anderson, and that we will see exosome capture and resulting benefit to the patients. If these scenarios come about, then we really have a tiger by the tail here!