Powerful stem cells harnessed to search for cancer metastasis

Stem cells that act as seek-and-destroy missiles appear to be able to find cancer wherever it hides out – at least, so far, in animals.

This novel approach at gene therapy, reported by researchers from The University of Texas M. D. Anderson Cancer Center, may have use in a wide variety of both solid and blood cancers.

“This addresses our great need for cancer gene therapies aimed at curbing the metastatic spread of cancer cells,” says Michael Andreeff, M.D., Ph.D., professor in the Departments of Blood and Marrow Transplantation and Leukemia. “It is exciting because it is an entirely new way of thinking about gene therapy and not just a twist of an old idea.”

Andreeff will present both the concept, and a series of supporting animal studies, at the annual meeting of the American Association for Cancer Research.

The novel strategy takes advantage of the fact that tumors attract a certain kind of stem cell, mesenchymal progenitor cells (MSC), which act as the body’s natural tissue repair system. These unspecialized cells migrate to an injury by responding to signals from the area, and there they develop the kind of connective tissue that is needed to repair the wound.

But they also respond to tumors — often characterized as “never healing wounds” — which “call” the stem cells to help build up normal tissue that is needed to support the cancer, says Andreeff.

Andreeff and a team of researchers removed a small number of MSC from the bone marrow, expanded them in the laboratory, and genetically altered the stem cells with a variety of therapeutic genes. When intravenously injected into tumor-bearing mice, the millions of engineered stem cells engraft in the cancer, and activate their genetic payload, which then attacks the cancer.

Andreeff will present animal data suggesting that gene modified MSC can inhibit the growth of leukemias, lung metastases of melanomas and breast cancer, ovarian and brain tumors. For example, MSC gene therapy cured 70 percent of mice implanted with one kind of human ovarian cancer. So far, researchers delivered interferon alpha and beta, and an oncolytic (tumor-destroying) virus into the tumors.

“This drug delivery system is attracted to cancers, both primary and metastatic, and anti-tumor effects are observed when the cells integrate into the tumor microenvironment” says Andreeff. “The most important discovery here is that these cells are capable of migrating from the bone marrow or blood circulation selectively into tumors and produce anti-tumor agents only at the sites of these tumors and their metatasis.”