The Columbia researchers will investigate how two experimental vaccine therapies induce both local and broad immune responses in patients who have intractable malignant tumors, within a clinical trial that is funded by other sources.
Recent evidence suggests that cancers suppress the body's immune responses at the site of tumor growth. This explains why tumors grow and metastasize undetected by the body's immune system. Substantial research now is focused on developing therapeutic vaccines that could induce the patients' immune systems to identify and attack the tumors. Most of these experimental vaccines contain specific antigens (pathogens) that are delivered to the tumor site, where they get inside the tumor cells. Then immune T cells learn to recognize this antigen and attack it, killing its host, the tumor cell. Another approach, however, is based on evidence that immune T cells may lay dormant in the presence of a tumor because the tumor does not transmit "co-stimulatory" signals that are needed to activate T cells. The Columbia researchers hypothesize that delivering a "co-stimulatory" molecule, rather than an antigen, into the tumor cells might provide a general, more effective way to galvanize T cells to attack the tumor cells.
The investigators have developed two experimental therapeutic vaccines to deliver co-stimulatory molecules to tumor cells and are testing the vaccines' safety in clinical studies supported by the National Cancer Institute (NCI). Both vaccines consist of fowlpox virus, which is not harmful to humans but can insert itself into tumor cells and deliver the co-stimulatory molecule into the tumor cells. (One vaccine contains a single co-stimulatory molecule, the other contains three.) Once inside the tumor cells, the co-stimulatory molecule(s) transmit their signals to patients' immune T cells, which then attack the tumor cells. The NCI-supported study is determining the two vaccines' safety in 36 patients with intractable tumors that have not responded to any available therapy. The patients are randomized to receive one vaccine or the other.
With Dana support, the researchers will measure participating patients' T cell levels before and after vaccine administration, to determine the extent to which the vaccines stimulate T cell function at the tumor site and whether this leads to generalized (systemic) anti-tumor immunity throughout the patients' bodies. The researchers also will try to identify predictors of patients' immunologic response. The clinical trial to which this study will be attached has been approved by Columbia's Institutional Review Board, the National Institutes of Health, and by the Food and Drug Administration which authorizes human testing of experimental drugs and biologicals.