Implantable Vaccine Eliminates Melanoma Tumors in Mouse Model

Cancer researchers have implanted plastic disks impregnated with tumor-specific antigens under the skin of a mouse model to reprogram the animals' immune system to attack tumors.

Investigators at Harvard University (Cambridge, MA, USA) employed highly permeable 8.5-mm disks made of an FDA-approved biodegradable polymer. The disks were impregnated with various combinations of an inflammatory cytokine, immune danger signal, and tumor lysates to control the activation and localization of host dendritic cell populations.

Results published in the November 25, 2009, issue of the journal Science Translational Medicine revealed that vaccination by this method maintained local and systemic cytotoxic T lymphocyte responses for extended periods while inhibiting FoxP3 T cell regulatory activity during antigen clearance, resulting in complete regression of distant and established melanoma tumors.

In human disease, alterations in numbers of regulatory T cells – and in particular those that express Foxp3 – are found in a number of disease states. For example, patients with tumors have a local relative excess of Foxp3 positive T cells which inhibits the body's ability to suppress the formation of cancerous cells. Conversely, patients with an autoimmune disease such as systemic lupus erythematosus (SLE) have a relative dysfunction of Foxp3 positive cells.

Senior author Dr. David J. Mooney, professor of bioengineering at Harvard University, said, "This work shows the power of applying engineering approaches to immunology. By marrying engineering and immunology we have taken a major step toward the design of effective cancer vaccines. This approach is able to simultaneously upregulate the destructive immune response to the tumor while downregulating the arm of the immune system that leads to tolerance. In cancer, this latter arm is typically a limiting feature of immunotherapies, since it can extinguish vaccine activity and afford tumors a degree of protection."

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