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How Cancer Beats the Immune System

Recent scientific discoveries have provided researchers with a better understanding of the interactions between cancer and the host immune system. As a result, therapeutic strategies to address cancer have shifted to an immunological approach over the past few years, with Dendreon Corporation’s (DNDN) Provenge becoming the first approved therapy of this type back in April of 2010. By stimulating a patient’s own immune system to target prostate cancer cells, Phase III clinical trials showed that treated patients lived an average of 4.1 months longer than patients given the control autologous cell treatment.

Unfortunately, cancer has ways of beating these immunological approaches and ultimately taking the lives of patients. Recent research has shown that cancer tumors excrete vesicular structures, known as exosomes, which have an immunosuppressive effect on the body. The result is suppression of the body’s own immune system and counteraction of many immunological cancer treatments that rely on a natural immune response.

Exosomes’ Effect on the Immune System

Cancerous tumors release exosomes that carry a large array of proteins from the originating cell, and can have a detrimental effect on the immune system. For example, tumor-secreted exosomes have been shown to counteract the beneficial effects of antitumor T cells and dendritic cells commonly used in immunotherapies.

According to an abstract, entitled Tumor-released exosomes and their implications in cancer immunity, published in 2007 and archived on Nature:

Tumour cells release vesicular structures, defined as microvesicles or exosomes, carrying a large array of proteins from their originating cell. The expression of antigenic molecules recognized by T cells has originally suggested a role for these organelles as a cell-free antigen source for anticancer vaccines. However, recent evidence shows that tumour exosomes may also exert a broad array of detrimental effects on the immune system, ranging from apoptosis in activated antitumour T cells to impairment of monocyte differentiation into dendritic cells and induction of myeloid suppressive cells. Immunosuppressive exosomes of tumour origin can be found in neoplastic lesions and sera from cancer patients, implying a potential role of this pathway in in vivo tumour progression.

Exosomes accomplish these effects using escape mechanisms to silence their immunogenic profile and activate immunosuppressive/deviating pathways. The resulting environment supports the formation of cancer metastasis, with the quantity of exosomes in circulation positively correlating with disease progression. Immunological approaches to cancer treatment, using T cells or dendritic cells, may therefore be less effective in advanced-stage patients.

Innovative Solution to Removing Exosomes

Aethlon Medical Inc. (AEMD) is a medical device company that has developed candidate diagnostic and therapeutic solutions to address exosomes. Its Enzyme Linked Lectin Specific Assay (ELLSA) is an assay that identifies the presence of cancer exosomes, and once identified, the Aethlon Hemopurifier® provides a device mechanism to target the elimination of tumor-secreted exosomes from the entire circulatory system using a dialysis-like process.

Potential Investment Opportunity

While Aethlon has been advancing the Hemopurifier® as an adjunct to optimize Hepatitis C drug therapies, the company recognizes the potential of the Hemopurifier® to augment the benefit of emerging immunological cancer treatments, including those developed by companies like Northwest Biotherapeutics Inc. (NASDAQ:NWBO) and ImmunoCellular Therapeutics Ltd. (NYSE:IMUC). After all, the removal of immunosuppressive exosomes would presumably increase the benefit of emerging therapies to stimulate the immune response. Importantly, the company was awarded a U.S. Patent last fall that covers the external removal of exosomes and other microvesicles from the bloodstream, placing Aethlon on the leading edge of the movement to effectively deal with these troublesome particles.

With Dendreon’s Provenge alone serving over 800 parent accounts and generating more than $325 million in 2012 product revenues, there’s a significant market opportunity for the company’s diagnostic test and blood purification device given its modest $15 million market capitalization. Investors will be watching for results from current clinical programs and the initiation of future studies related to cancer.

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