Tissue-Engineered Cancer Metastasis to Improve the Abscopal Effect and Cancer Immunotherapy in Melanoma
Abstract
Our application will address the Fiscal Year 2015 Peer Reviewed Cancer Research Program topic area "melanoma and other skin cancers" and the Military Relevance Focus Area of "Gaps in cancer treatment that may affect the general population but have a particularly profound impact on the health and well-being of military members, Veterans, and their beneficiaries." Cancer immunotherapy has generated exciting clinical data in many cancers, especially in melanoma. While some patients have long durable response to immunotherapy agents, most patients still suffer from disease relapse. Therefore, there is strong interest in the development of novel strategies to improve immunotherapy responses. One such approach is to use radiotherapy/radiosurgery in conjunction with immunotherapy. However, radiotherapy has many limitations and not every patient is eligible for radiosurgery. In this application, we aim to overcome these challenges by engineering cancer metastasis ex vivo (outside of the body), lethally irradiating them, and using them to improve cancer immunotherapy. We propose to evaluate our approach using mouse models of melanoma. We will first engineer melanoma lung metastases using patented tissue engineering techniques developed in our laboratory. These engineered metastases will be three-dimensional and closely mimic the human condition. The metastases will be lethally irradiated with high dose radiation. Following irradiation, they will be injected into mice bearing melanoma tumors and are undergoing immunotherapy. We will assess whether the engineered metastases can improve immune response to the existing tumor. In addition, we will compare the engineered metastases to spontaneous metastases in improving cancer immunotherapy. We also propose to engineered metastases where the tumor environment is pro-inflammatory, which will facilitate and increase the immune response. We will assess whether such metastases can further improve immunotherapy response. Lastly, we propose to develop techniques to engineer metastasis using patient s tumor cells. Such techniques will enable the rapid clinical translation of our approach. Our proposed research has the potential to significantly advance the treatment for metastatic melanoma as well as other cancers that benefit from cancer immunotherapy. It can lead to increase response rates and increased duration of response to cancer immunotherapy agents. This will directly translate into improved survival and quality of life in cancer patients. Our work is particularly important for current and former members of the military, as melanoma as well as several other cancers disproportionally affect the military members.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610530
Entities
People
- Zhuang Wang
Organizations
- United States Army
- University of North Carolina at Chapel Hill