Exosomes as a means of immune escape

San Diego, CA -

It has been widely known for more than a century that activation of immune responses can in some situations cause tumors to regress. This has been the basis for thousands of clinical trials using various proteins as therapeutic vaccines, which aim at inducing the immune system to kill cancer. These trials have had mixed results. One possibility for the mediocre performance is that they were not targeting the tumor stem cell. It is also known that the tumor mass is maintained by a small population of "tumor stem cells" that display immunologically distinct proteins than the mass of the tumor. Partially because of antibodies available to tumor stem cells, the company OncoMed entered a > $1 billion co-development deal with Glaxo.

However, there is another component to this. In a recent paper (Exosomes as a tumor immune escape mechanism: possible therapeutic implications. J Transl Med. 2008 Jul 22;6(1):37) the case is made that tumors secrete nano-sized vesicles called "exosomes" which specifically induce apoptosis of T cells that recognize tumor antigens. Most interestingly, the paper uses exosomes to explain results from the 1960s of Hellstrom's group where antigen-specific "blocking factors" were reported in the plasma of patients with cancer.

The possibility of cancer stem cells specifically inducing apoptosis of T cells attempting to recognize them is supported by a paper demonstrating expression of the cancer stem cell marker CD133 on exosomes (Marzesco et al. Release of extracellular membrane particles carrying the stem cell marker prominin-1 (CD133) from neural progenitors and other epithelial cells. J Cell Sci. 2005 Jul 1;118(Pt 13):2849-58).

Perhaps most interesting about the paper is the possibility of using an existing device, Aethlon Medical's Hemopurifier(TM), which has already been used in clinical trials, to remove these exosomes from the blood of cancer patients. In a recent press release, Aethlon was cited as saying:

"In studies led by Dr. Douglas Taylor at the University of Louisville, 60% of circulating exosomes were removed from the blood of ovarian cancer patients during first pass (approximately 10-minutes) through a small scale Hemopurifier®. The capture data was consistent over the course of five different in vitro blood studies. The ability to reduce circulating exosomes would likely reverse immune suppression and increase patient responsiveness to both immunotherapy and chemotherapy"

Aethlon is a San Diego publicly traded biotechnology company, whose website is www.aethlonmedical.com.

We at StemCellPatents.com eagerly anticipate progress on the possibility of using a dialysis-type set up for removing immune suppressive components from the blood of cancer patients. By merging this technology with advances in identification of immune epitopes in cancer stem cells, we believe substantial progress in the area of cancer immunotherapy can be made.