SAN DIEGO - January 15, 2013 (Investorideas.com newswire) - 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.
References
(1)
http://www.breastcancer.org/symptoms/understand_bc/statistics
(2) King HW, Michael MZ and Gleadle JM. Hypoxic enhancement of exosome release by breast cancer cells. BMC Cancer 2012; 12:421.
(3) 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.
(4) 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.
(5) 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.
(6) 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.
(7) 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.
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.
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 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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