Cancer Nexus Blog

The UMass Cancer Center Pilot Grant Program fosters exciting science and innovation in cancer research at UMass Chan Medical School. The goal of the program is to provide support for cancer discoveries at their earliest phase, and facilitate further development of projects to a stage when they can obtain external support.

In its inaugural year, The UMass Cancer Center Pilot Grant Program awarded funds for three projects. One of the awards went to the team of John Harris, MD, PhD, chair and professor of dermatology, and Anastasia Khvorova, PhD, the Remondi Family Chair in Biomedical Research and professor of RNA therapeutics, for their research project entitled "Does intratumoral injection of AIM2 siRNA enhance the response of immune checkpoint inhibitor for melanoma?"

The award allows Dr. Harris, who is interested in developing treatments for dermatologic disorders and skin cancers such as melanoma, and Dr. Khvorova, who specializes in the chemical biology of therapeutic RNAs, to extend their long-time collaboration. The project seeks to improve treatments for a large fraction of melanoma patients who do not respond well to immunotherapy.

Using their combined expertise, Drs. Harris and Khvorova will use a small interfering RNA (siRNA) designed to modulate expression of the gene AIM2 in melanoma tumors. The funded pilot project aims to determine whether modulation of this gene will modify the tumor microenvironment to make it accessible to immunotherapy, essentially converting a "cold" melanoma tumor (one that is resistant to immunotherapy drugs) to a “hot” tumor, and significantly enhance the tumor’s response to immunotherapy (in particular, to inhibitors of the immune checkpoint protein PD-1).

Although previous approaches had endeavored to develop siRNA therapeutics for cancer several years ago, they did not fare well in the clinic owing to challenges in developing an effective system to deliver the siRNAs to the patient’s cells. But that has recently changed with advances in oligonucleotide chemistry that have enhanced delivery. The siRNA technology platform used in this project has only recently advanced enough to allow robust and sustained modulation of gene expression in tumors. As Dr. Khvorova points out, “This would not have been possible a couple of years ago.”

Watch Dr. Khvorova’s discussion of the funded pilot project below.