SAN DIEGO - December 7, 2012 (Investorideas.com newswire) - Aethlon Medical, Inc. (
OTCBB: AEMD), today released the following note authored by its Chairman and CEO, Jim Joyce.
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. Annette Marleau (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 cancer1. 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%2. 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 Nature Medicine, Dr. David
Lynden'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 vessels3. 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. Joshua Hood and colleagues at
Washington University 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 foci4. 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 cells5.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 exosomes6. 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.
References
1 Logozzi M, De Milito A, Lugini L, Borghi M, Calabrò L, Spada M,
Perdicchio M, Marino ML, Federici C, Iessi E, Brambilla D, Venturi G,
Lozupone F, Santinami M, Huber V, Maio M, Rivoltini L, Fais S. High
levels of exosomes expressing CD63 and caveolin-1 in plasma of melanoma
patients. PLoS One. 2009;4(4):e5219.
2
http://www.cancer.org/cancer/ skincancer-melanoma/detailedguide/ melanoma-skin-cancer -survival-rates
3 Peinado H, Aleckovic M, Lavotshkin S, Matei I, Costa-Silva B,
Moreno-Bueno G, Hergueta-Redondo M, Williams C, GarcÃa-Santos G, Ghajar
C, Nitadori-Hoshino A, Hoffman C, Badal K, Garcia BA, Callahan MK, Yuan
J, Martins VR, Skog J, Kaplan RN, Brady MS, Wolchok JD, Chapman PB, Kang
Y, Bromberg J, Lyden D. Melanoma exosomes educate bone marrow
progenitor cells toward a pro-metastatic phenotype through MET. Nat
Med. 2012 Jun;18(6):883-91.
4 Hood JL, San RS, Wickline SA. Exosomes released by melanoma cells
prepare sentinel lymph nodes for tumor metastasis. Cancer Res. 2011 Jun
1;71(11):3792-801.
5 Parolini I, Federici C, Raggi C, Lugini L, Palleschi S, De Milito
A, Coscia C, Iessi E, Logozzi M, Molinari A, Colone M, Tatti M,
Sargiacomo M, Fais S. Microenvironmental pH is a key factor for exosome
traffic in tumor cells. J Biol Chem. 2009 Dec 4;284(49):34211-22.
6 Marton A, Vizler C, Kusz E, Temesfoi V, Szathmary Z, Nagy K,
Szegletes Z, Varo G, Siklos L, Katona RL, Tubak V, Howard OM, Duda E,
Minarovits J, Nagy K, Buzas K. Melanoma cell-derived exosomes alter
macrophage and dendritic cell functions in vitro. ImmunolLett. 2012
Nov;148(1):34-8.
About Aethlon Medical
The Aethlon Medical mission is to create 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 therapeutics that target the selective removal of disease
enabling particles from the entire circulatory system. The Aethlon
ADAPT™ product pipeline includes the Aethlon Hemopurifier® to address
infectious disease and cancer; HER2osome™ to target HER2+ breast cancer,
and a medical device being developed under a contract with DARPA that
would reduce the incidence of sepsis in combat-injured soldiers and
civilians. For more information, please visit
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 company can successfully protect its intellectual
property, that removal of exosomes from the human body will impact or
lead to successful treatment of cancer, or that exosomes are the cause
of tumor growth and progression, 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 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.
Contacts:
James A. Joyce
Chairman and CEO
858.459.7800 x301
jj@aethlonmedical.com
Jim Frakes
Chief
Financial Officer
858.459.7800 x300
jfrakes@aethlonmedical.com
Marc Robins
877.276.2467
mr@aethlonmedical.com
Published at Investorideas.com Newswire
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