Dec. 7, 2012
Aethlon Medical, Inc.
(OTCBB: AEMD), today released the following note authored by its Chairman and CEO,
At Aethlon Medical, our focus is to create revolutionary medical devices that save lives. In the treatment of Hepatitis C (HCV) infected individuals, we have demonstrated that our Hemopurifier® synergistically combines with drug therapy to accelerate the achievement of undetectable viral load. In cancer, I envision our opportunity to save lives will be driven by the discovery that our Hemopurifier® can addresses a therapeutic target that plays a pivotal role in cancer progression, yet remains beyond the reach of drug therapies. The target? Microvesicles known as exosomes, which are particles secreted by tumors underlying a wide-range of cancers.
When we first initiated our tumor-derived exosome research, it was based on a belief that these particles were immunosuppressive, much like glycoproteins that shed from HIV and other viral pathogens. However, the medical community consensus at the time was that exosomes had no biological function other than to discard cellular debris. Today, tumor-derived exosomes are known to suppress the immune response in cancer patients. Beyond possessing immunosuppressive properties, tumor-derived exosomes facilitate tumor growth, metastasis, and the development of drug resistance. Such deleterious effects underlie the pathogenesis of cancer, and as a result of our early research we have been able to obtain broad patent protection in the field. By addressing this unmet medical need, our objective is to deliver a medical device that improves the benefit of cancer therapies without adding drug resistance or interaction risks.
As more and more medical institutes establish exosome research programs, we benefit from new discoveries that will help us to understand which forms of cancer are most likely to benefit from our technology. In this regard, Dr.
(our Director of Tumor Immunology) provides the following review on recent discoveries that describe the implication of exosomes in metastatic melanoma, a form of cancer whose 5-year survival rate is less than 20%.
Exosomes As Therapeutic Targets In Metastatic Melanoma
Exosomes are nano-sized microvesicles released in large quantities by cancer cells that are key culprits in the pathogenesis of several cancer types. Exosomes are now recognized as biological delivery vehicles for communication between cells in almost every system of the body investigated to date. In the area of oncology, cancer derived exosomes are highly stable "packages" released from tumors that transport proteins and genetic material from their originating tumor cells to distant sites throughout the body to accelerate tumor progression. In melanoma patients, tumor-secreted exosomes serve as carriers of malignant proteins and their levels in circulation correlate with the aggressiveness of the cancer
. To date, cancer exosomes have been implicated in: a) immune suppression; b) enhancement of angiogenesis; and c) promotion of metastasis, which will be discussed below.
Owing to several recent publications that have defined their pathological roles in metastatic disease, melanoma exosomes are emerging as candidate therapeutic targets. Metastatic (stage 4) melanoma, the most aggressive form of skin cancer, has a five-year survival rate of only 15-20%
. This disease continues to be a challenge to treat, as the current standard treatments have proven to be ineffective and/or highly toxic. Since patients afflicted with metastatic melanoma have suppressed immune systems due to tumor- and drug-related effects, the efficacy of novel immunotherapeutic solutions is limited and only small percentages of patients experience durable responses and extended survival. Thus, the development of novel treatments to reliably bolster anti-cancer immune responses remains an urgent clinical objective.
Recent scientific studies have defined the importance of melanoma exosomes in the progression of cancer, thereby providing the rationale for targeting tumor-derived nano-vesicles therapeutically. In a 2012 publication in the prestigious journal
's group at Weill Cornell Medical College and their colleagues reported that melanoma tumors release exosomes that condition metastatic sites for growth of tumors and their supporting blood vessels
. This publication also identifies a correlation between high exosome concentrations in circulation with advanced disease and poor prognosis of patients. This knowledge reinforces the concept that a strategy for eliminating circulating exosomes could be beneficial for addressing metastatic disease.
A pivotal publication by Dr.
and colleagues at
School of Medicine showed that melanoma exosomes migrate to lymph nodes and alter the biochemical milieu to allow lodging of cancer cells in the establishment of metastatic foci
. Once again, this study suggests that systemic clearance of melanoma exosomes could interrupt the "messenger system" underlying metastasis. Along these same lines, a study by Parolini and colleagues in
The Journal of Biological Chemistry
demonstrated that melanoma exosomes serve as delivery vehicles for spreading malignant proteins from high aggressive metastatic cells to less aggressive cancer cells
.This article raises the concept that exosomes from a primary tumor can transfer their cargo to distant organs, thereby allowing the malignancy to spread.
Experiments have also demonstrated that the functions of immune cells are impaired by melanoma exosomes
. Since the immune system is responsible for recognizing and destroying cancer cells, exosomes thereby manipulate immunity to allow tumors to grow unchecked. Additionally, since immunotherapy is administered to bolster the patient's endogenous immune response, melanoma exosomes impair the effectiveness of these treatments. On this basis, a device strategy for removal of circulating exosomes could be implemented to reverse immune dysfunction in order to improve the effectiveness of standard of care treatments against metastatic melanoma.
Given these recent scientific developments that reveal broad tumor growth promoting and immune inhibitory effects of melanoma exosomes, there is a strong impetus for moving forward with therapeutic targeting options, which do not exist to date. Clinical studies are needed to define the impact of exosomes in metastatic melanoma and to offer promising new treatment solutions that are urgently needed.