Researchers at The University of Texas M. D. Anderson Cancer Center have perfected a delivery system for anticancer treatment that zeroes in on a tumor and becomes part of its supporting tissue. This new “cellular vehicle” then pumps drugs directly into cancer cells to disable them, but leaves normal tissue alone.
They say their study, published in the Journal of the National Cancer Institute, is a proof of principle, conducted in mice, that shows this kind of strategy could be promising when developed for human use.
“This is the most effective homing strategy seen to date, much better than any viral delivery strategy tested so far,” says Michael Andreeff, M.D., Ph.D, professor in the Departments of Blood and Marrow Transplantation and Leukemia. “It is remarkable that these cells can find tumors wherever they are and become part of them.”
The new approach uses human mesenchymal stem cells (MSC), the body's natural tissue regenerators. Tissue that is injured sends signals to these unspecialized, progenitor cells, and they, in turn, migrate to the damage and morph into whatever kind of tissue — bone, fat, muscle, cartilage, tendons — is needed to repair the wound.
Tumors, however, are "never-healing wounds" that also signal these stem cells, and then use them to help build up “stromal,” or connective tissue, that structurally supports and nurtures tumor growth, says Andreeff. “Tumors constantly remodel their architecture with the help of these special stem cells.”
Andreeff, first author Matus Studeny, M.D., who was a research fellow in Andreeff’s lab, and a group of six other researchers turned the tables on cancer, taking advantage of a tumor's ability to attract these stem cells.
They designed a novel delivery system by isolating a small quantity of MSC from bone marrow, and then greatly expanded those cells in the lab. The researchers then used a virus to deliver a particular gene that has therapeutic action against cancer into the stem cells. When given back through an intravenous injection, the millions of engineered mesenchymal progenitor cells engraft where the tumor environment is signaling them, and then activate the therapeutic gene.
The team has already tested the system in a number of different solid cancers, as well as in leukemia, to deliver different “payloads,” but in this study, they looked at whether MSC engineered to carry interferon beta could treat mice that were implanted with human breast cancer or human melanoma.
Interferon beta can inhibit cancer growth in laboratory tests, but is excessively toxic and short-lived when used at high doses as a therapy in patients, says Andreeff. The team tested whether MSC engineered to express an interferon beta gene could provide a sustained and targeted effect directly to cancer cells.
For each of the two cancer types, the researchers tested three groups of mice against each other: one was an untreated control group; another was injected with interferon beta daily under the skin for three weeks; and the third received three weekly doses of intravenous MSC engineered to express the interferon beta payload.