Active Immunotherapy Blocks Formation of Tumor Blood Vessels

Cancer researchers using a novel method based on tumor cells taken from the patient, which have been engineered to secrete immune stimulating molecules and then returned to the patient, have found that this approach has a disruptive effect on the tumor's ability to create new blood vessels.

Investigators at the Dana-Farber Cancer Institute (Boston, MA, USA) vaccinated a group of clinically responsive cancer patients with lethally irradiated, autologous tumor cells engineered to secrete granulocyte‐macrophage colony stimulating factor (GM-CSF). In addition, the patients received an antibody blockade of cytotoxic T lymphocyte–associated antigen-4 (CTLA-4).

Results published in the December 15, 2010, issue of the journal Cancer Research revealed that this type of immunotherapy stimulated a response in patients that caused the selective destruction of tumor blood vessels. Antibodies to angiopoietin-1 and angiopoietin-2 were generated that blocked Tie-2 binding, downstream signaling, endothelial cell tube formation, and macrophage chemotaxis.

"It appears that the body's own immune system can be used to develop a new way to block angiogenesis,” said senior author Dr. Glenn Dranoff, associate professor of medicine at the Dana-Farber Cancer Institute. "Angiogenesis involves multiple factors, and our studies suggest that it may be advantageous to target several of these at the same time, rather than only focus on one factor, such as vascular endothelial growth factor. Substantial evidence indicates that inhibiting angiogenesis is a validated strategy for cancer therapy, but current approaches are in need of further improvements.”

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Dana-Farber Cancer Institute