Next Generation Immunotherapy for the Treatment of Melanoma

PI: Dr. M. Karen Newell-Rogers, Ph.D.

Funded by CU Advanced Industries Proof of Concept Grant

Cancer remains one of the leading causes of death world-wide and the discovery of new, effective cancer treatment therapies is a critical unmet need. One of the most promising new strategies in cancer treatment has been the development of therapies that target the body’s own immune system, or its components, to fight the disease. Promising approaches in this field of immunotherapy include antibodies against cancer cell components, therapeutic cancer vaccines, whole cell therapies and, most recently, drugs that target “immune checkpoint” molecules.

This latter group of immunotherapy drugs which target immune checkpoint molecules is designed to stimulate wanted or inactivate unwanted immune responses against cancer cells. Well known immune checkpoint inhibitor ("ICI") drugs include YervoyTM, a blockade for the molecule CTLA-4, and OpdivoTM and KeytudaTM, drugs designed to block the unwanted PD1:PDL1 interaction. A common feature of these ICI drug therapies is their inactivation of unwanted immune cells that seem to protect the cancer tumor from an effective anti-tumor response.

The results of cancer treatments using ICIs have been both impressive, and disappointing. For example, cancer-free survival rates for patients with advanced melanoma treated with ICI drugs are in the range of 30% to 40%. Although a positive outcome for some melanoma patients, the question remains why a large percentage of melanoma patients, roughly 60% to 70%, do not respond favorably to otherwise blockbuster ICI drugs.

 Professor M. Karen Newell-Rogers, PhD, has spent much of her academic career studying the complex mechanisms of cell death. Her research portfolio has included the identification of an important connection between the selective engagement of Major Histocompatibility Complex-encoded Class II Molecules (MHCII) and cell death. Specifically, discovery that MHCII expression at the cell surface provides a trigger mechanism for T-Cell stimulation, which is known to serve as a key cellular event in an anti-tumor immune response, and can under certain circumstances cause cell death of the MHC Class II expressing cell.

In addition to the PI's research on MHCII expression and cell death, the PI (and her research associates) has also previously invented and synthesized a specialized, custom peptide capable of serving as an immune modulating therapy that, in conjunction with the cell's expression of MHCII, enhances the likelihood of death of unwanted cells, including tumor cells.

This proof of concept ("POC") study is designed to prove why the success rate for ICI drugs in treating melanoma is limited to 30% - 40% and to prove that ICI drugs in combination with a targeted peptide therapy invented by Dr. M. Karen Newell-Rogers (subject to patents held by the University of Colorado ("CU")) will substantially improve the success rate of ICI drugs in the treatment of melanoma. To date, the PI has successfully demonstrated that the targeted peptide technology is effective in removing unwanted cells, including tumor cells, in a variety of systems. Building on this principle, we are requesting AIA grant funds to expand these findings to determine the effectiveness of the peptide as a co-treatment to augment current efficacy of ICI therapies to improve ICI drug effectiveness in treating melanoma to greater than its current 30%-40% success rate. Since the current stage of the peptide technology research has not yet achieved proof of concept, the availability of private sector funds is limited. AIA funds in support of this POC are intended to catalyze private sector interest in the peptide technology following successful proof of claim. We hope to prove that use of this peptide along with ICI drug therapies could radically advance success rates in treating melanoma and potentially other cancers.