Are Exosomes the Next PD-1 in Cancer Research?


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OTC:BB:AEMD / NYSE:MRK / NYSE:BMY
04/30/2014 [ACCESSWIRE]

Whitefish, MT / April 30, 2014 / PD-1, or programmed death protein 1, is certainly a hot button in the field of oncology, with the new immune checkpoint inhibitors pegged by many as part of a wave of new therapies to meet areas of great unmet medical need in cancer treatment.  Merck & Co. (NYSE: MRK) has received the coveted FDA "breakthrough" designation for its PD-1 inhibitor lambrolizumab, putting it in a position to vie for the lead with Bristol-Myers Squibb's (NYSE: BMY) antibody nivolumab.  Both companies have reported impressive results on their drugs for several cancer types, either as a monotherapy or in combination treatments, including melanoma and non-small cell lung cancer.

The excitement around potentially paradigm-shifting new therapeutics was also highlighted in a recent article in the publication Trends in Molecular Medicine, titled "Extracellular Vesicles: Emerging Targets for Cancer Therapy". The article, authored by a team of researchers from Harvard Medical School, Massachusetts General Hospital and University of Oxford, details the importance of exosomes (also called "extracellular vesicles," "EVs" or "cell-derived vesicles") and the captivating role that they play in cellular communication and homeostatic health.  All nomenclature aside, exosomes could be the next PD-1 inhibitors for cancer and other diseases and conditions as part of the next generation of novel therapeutics. 

Exosomes were thought of simply as cellular debris until recently, when scientists started to understand that exosomes are essentially a coded language established by the body's cells that carry critical genetic information about cells of all types, including tumor cells.  While more human trials are required to validate the in vivo and in vitro lab work, exosomes have been shown to play an active role in the pathogenesis of cancer on many fronts, including the earliest stages of signaling and angiogenesis, meaning that increased numbers of exosomes could hold a vital key in early detection like never before. 

In fact, earlier research indicates that PD-1 itself is expressed and transported by dendritic cell-derived exosomes. As you read through the discussion below, keep this in mind. Exosome-based therapies may yet prove to intertwine with PD-1 inhibition. If this ends up being the case it could create a perfect storm in the world of emerging cancer therapeutics. 

Other realizations about the role of exosomes are groundbreaking.  For example, as the article notes, 

"One of the most striking features of tumour-derived EVs is their potential to facilitate formation of the pre-metastatic niche, the specialised microenvironment that forms at a distant organ site in preparation for future tumour metastasis." 

Vesicle shedding is also theorized to contribute to drug resistance and immunosuppression as cells "fool" the body into believing they are native, rather than dangerous.  Breaking the cypher to understand how cells are "speaking" to each other or recognizing where tumors plan to metastasize before they do, in combination with other EV-inhibiting therapies to interrupt the cell communication network, would revolutionize how cancer is treated today. 

These types of discoveries have opened the door to countless applications related to exosomes, including diagnostics and treatment for not only cancer but also bacterial and viral infections, neurodegenerative diseases and many more.  Moreover, because exosomes are found in basically every bodily fluid (i.e. blood, lymph, urine, saliva, etc.), there are strong implications that disease detection can become vastly simplified by testing fluids, as opposed to invasive and costly procedures such as biopsies.

Throughout the last decade or so, scientists, are starting to dial-in the importance of exosomes and building on the pioneering work of individuals like Dr. Douglas Taylor.  Dr. Taylor, Chief Scientific Officer of Exosome Sciences, Inc., a wholly-owned subsidiary of Aethlon Medical Inc. (OTCBB: AEMD), published the first article describing circulating tumor exosomes/microvesicles in 1979 and is widely recognized as one of the world's foremost experts in exosomes and their function. 

The Trends in Molecular Medicine publication specifically mentions Aethlon's affinity plasmapheresis  ADAPT(TM) platform, which features a unique device called the Hemopurifier(R), for its potential to capture specific exosomes during extracorporeal dialysis to improve cancer therapies.  More succinctly, the authors stated, 

"For example, in human epidermal growth factor receptor-2 (HER-2) overexpressing breast cancer, where HER-2-expressing EVs have been shown to interfere with therapy and are associated with tumour aggressiveness, anti-HER-2 antibodies could be used to remove HER-2-expressing EVs from circulation with the aim of improving therapeutic outcome. In principal, this approach could be tailored for other tumour types, as long as the tumour cell-derived EVs are enriched for tumour-specific proteins."

The old adage of "where there's smoke, there's fire," seems appropriate in the case of exosomes, as elevated levels of the microvesicles say that something is not right in the body.  The Trends in Molecular Medicine article makes the point very clear and adds to a growing library of evidence about the relevance of exosomes in disease management.  Major pharma may be mostly looking over the fence at exosomes' diagnostic and therapeutic uses at the moment, but it is highly probable that the trend to utilize technologies targeting exosomes will start on a non-linear path in the near future with additional clinical validation as the new wave of therapies continues to roll in.

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