Miles 4 Melanoma

I am honored to inform you that a co-sponsored 2007 Career Development Grant has been awarded in memory of George Madzia. This first-year grant is awarded to Dr. Gregory Lesinski at The Ohio State Universitry, and will be listed in our announcement and promotions as: Award in Memory of Brian Anderson, Tom Butler, Dr. R. Heath Scott, George Madzia, Karl Osterlof, Bruce Schocken, Bob Whitman, and George A. Wilkins.

Dr. Leskinski’s project is titled: The Role of Suppressors of Cytokine Signaling (SOCS) in Mediating the Anti-Tumor Properties of Interferon-alpha (IFN-?). [Below is] a summary of his research project.

Sandy, we are indebted to you, your family, and friends for making this first-year grant in George Madzia’s memory possible. Thank you from all of us.

Bill Marsch
The Melanoma Research Foundation

Dr. Gregory Lesinski – The Ohio State University; Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical GeneticsThe role of suppressors of cytokine signaling (SOCS) in mediating the anti-tumor properties of interferon-alpha (IFN-?).

Award in Memory of Brian Anderson, Tom Butler, Dr. R. Scott Heath, George Madzia, Karl Osterlof, Bruce Schocken, Bob Whitman, and George A. Wilkins

Interferon-alpha (IFN-?) is a hormone made naturally by the body that can help the immune system recognize developing tumors. Synthetic IFN-? is also used as a treatment for patients with melanoma. In a small subset of patients, IFN-? can cure or control this disease, however the precise way it does this is not understood. IFN-? works against melanoma by making white blood cells of the immune system more effective at killing tumor cells. However, there is no way to predict if this drug will work in every person. Doctors often give IFN-? at very high doses, and because of this, toxic side effects can occur, and patients stop taking this medicine early. IFN-? works by binding to a receptor on the outside of a cell, and causes a “domino-like” effect to other proteins inside the cell. This domino effect caused by IFN-? can be stopped by a group of proteins called the Suppressors Of Cytokine Signaling or “SOCS,” that act as brakes to stop the IFN-? signal. We think that SOCS proteins are making cancer patients respond less to IFN-? by stopping the effects of this drug on white blood cells.

We have shown for the first time that IFN-? can cure melanoma in mice that lack a protein called SOCS1 (SOCS1 KO mice). Based on experiments done in our laboratory, we expect that two types of white blood cells (called CD8 T cells and dendritic cells) are important for curing SOCS1 KO mice with IFN-?. In our studies, SOCS1 KO mice with melanoma will be depleted of certain types of white blood cells and treated with IFN-?. These experiments will allow us to prove the specific cell type that is needed to cure SOCS1 KO mice with IFN-?. We will also be interested in testing what exactly is different about white blood cells from mice without SOCS1. For example, we will determine whether they are better at directly killing melanoma cells, or whether they make other proteins that increase the overall activity of the immune system against melanoma. We will also give normal mice melanoma and then transfer different types of white blood cells lacking SOCS1 into these mice before treating with IFN-?. Our goal is to figure out exactly how IFN-? cures melanoma in mice that do not have SOCS1. We believe this knowledge could be used to help the immune system of patients recognize and eliminate melanoma tumors.

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