The Wong Laboratory Research Program

Angiogenesis, host immunosurveillance, and matrix permissibility, are all host responses that can be influenced pharmacologically. Importantly, these host events are not subject to the promiscuous gene activation that can occur within tumor cells. This means that, unlike tumor cells that can turn on any gene or any genetic program to side step a therapeutics strategy, host tissue are locked down into an end differentiation pattern. This means that your stomach cannot make kidney cells or bone, however molecular analyses of tumors show that they can evoke genetic programs along these lineage lines within the same tumor. Thus, it may be impossible to truly attack a cancer cell, whereas devising a strategy to modulate the limited gene expression that occurs within the host cells is imminently possible.

Our laboratory program targets the host-tumor interface. We are looking at ways to use the host immune response to attack cancer, to turn down angiogenesis, and to make the matrix surrounding the tumors inhospitable to tumor growth or metastases.

Our immuno-regulation program looks at the trafficking of dendritic cells in and out of tumors. These dendritic cells (DC) are responsible for evoking a primary host response. That is, the ability of the host immune system to recognize a new antigen. In addition, we are testing this in people by preconditioning of patients prior to their immunotherapy with interleukin-2, and our hope here is that we can improve upon the curative response rate that we can get with this therapy in kidney cancer and melanoma.

We are working at understanding the molecular signature of the vasculature within tumors, with the hope of being able to target these specifically while leaving the host intact. There is now good evidence that tumors can evoke a unique and specific signature within the endothelial cells that make up the inner most lining of the blood vessels within the tumors. By understanding and identifying this signature then targeting specifically to that tumor becomes possible. We have already had success in doing so, and we continue to develop this to identify and to attack tumors specifically.

We are working on a molecule called Plasminogen Activator Inhibitor1 (PAI-1) which has the powerful dual ability to influence angiogenic response to tumors, and to modulate a tumor microenvironment. As for the latter, we have found PAI-1 inhibits the ability of tumors to invade, and that is done by changing the invasive potential of malignant tumors through the inhibition of the proteolytic enzymes that they secrete. These enzymes directly degrade the peri-tumor connective tissue, thereby both allowing a permissive environment for angiogenesis and for tumor invasion. We are specifically studying bladder cancer and prostate cancer, since these tumors rely on both angiogenesis and proteolysis for their malignant potential.

Our ultimate goal is to translate these finding into useful strategies that will help people. Every individual in our program can link between the research lab and patient clinics. For these reasons it is possible to quickly traverse the gap between bench and bedside and live up to our lab motto ; “Hope, Innovation, Ideas”.