Targeting cell fusion as possible way to repair organs, deliver cancer vaccines
ROCHESTER, Minn. -- Mayo Clinic cancer researchers have developed a way to biologically fuse living cells through the use of a genetically engineered cell membrane. This process, which Mayo researchers call "biofusion," could speed development of new tumor treatments and cancer vaccines.
The Mayo Clinic cancer researchers' study on biofusion appears in the current issue of Nature Biotechnology (http://www.nature.com/nbt/). The researchers report their new process kills cancer tumor cells, based on their successful treatment of mice into which human cancers were implanted.
Significance of the Mayo Clinic Cancer Research
"Our biofusion research represents a promising new technological platform for enlisting natural properties of fused cells to kill cancers, stimulate immune responses or repair damaged tissues," says Stephen Russell, M.D., Ph.D. Dr. Russell directs Mayo Clinic's Molecular Medicine Program and leads the Mayo Clinic Cancer Center's Gene and Virus Therapy Program.
The key to biological cell fusion is that two cells come into contact and the fusion proteins on the surface of one cell recognize a receptor on the other cell. This act of recognition triggers fusion of their respective outer lipid membranes. "It's like two bubbles merging into one bigger bubble," explains Dr. Russell.
With cancer, the fusion rules change, says Dr. Russell. When cancer cells fuse with each other the "big bubble" formed may grow dramatically -- containing up to 1,000 cancer cells -- and it is nonviable. The cancer cells therefore die.
This fact that fused cancer cells kill each other has been known for some years. The missing element has been a way to direct fusion partners to exploit this tendency and use it as a basis for anticancer treatment.
The ability to target fusion partners is important. If the wrong cells fuse, then healthy cells -- instead of cancer -- can be killed. "Our biofusion research brings a new level of control to the system so the right fusion matches are made to serve therapeutic ends," says Dr. Russell. "It offers a biotechnology platform that provides a way to choose and direct the agents of fusion by getting tumor cells to fuse with dendritic cells -- one cell type in the immune system. The result is biofusion that prompts the immune system to attack the tumor.
"This is important because the exploitation of cell fusion, whether for killing cancer cells, repairing damaged tissues or stimulating the immune system, depends on making sure that it is accurately targeted," he says.
The ability to fuse tumor cells to treat cancers is one application the Mayo Clinic cancer research team envisions for their biofusion platform.
Another possible application involves cancer vaccines that prevent cancer from progressing or developing. Current vaccine approaches involve taking dendritic cells from cancer patients, feeding the dendritic cells tumor antigens, and then reintroducing the dendritic cells into the patient's body and relying on the body's natural process of "instruction" to help the body create cells that attack cancer. In this natural system, dendritic cells present antigens to other immune cells in a way that effectively "teaches" them what they are to attack.
Dr. Russell believes the biofusion technology would be a better way of "feeding" the dendritic cells the information they need to "learn" what they are to attack.
"Biofusion would involve putting genes in the dendritic cells inside the body that will cause them to fuse directly into tumors at multiple sites in the patient," he says. He notes that Mayo Clinic cancer research colleague Richard Vile, Ph.D., last year successfully fused tumor and dendritic cells to create a hybrid of the two -- but it was not targeted. "So this is not blue-sky stuff. We know we can make the hybrid," says Dr. Russell. "Now we just have to get the targeting ability."
A third possible application, still in the concept stages for this targeted biofusion technology, involves stem cells. Because of their powerful generative and regenerative abilities, stem cells are used to repair damage in the bone marrow and to different organs such as the liver, brain and heart.
Recent research shows that some of the stem cells' repair properties come from their ability to fuse with cells that are naturally resident in the organs they are repairing. "For example, they repair the liver by fusing the cellular structures in the liver," Dr. Russell explains. "We may be able to exploit this new biofusion technology by genetically engineering stem cells so they fuse quickly and efficiently to a target site, and thereby direct the stem-cell repair process."
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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