Immunotherapeutic Targeting of Colon Cancer Vascularization to Achieve Long-Term Immunity Against Primary and Metastatic Disease
Abstract
Scientific Rationale and Objective: Tumor immunotherapy represents a promising therapy to treat patients with locally advanced and metastatic colon cancer. This type of strategy is intended to be a safer and more effective alternative to the standard aggressive and toxic treatment options currently available to patients. Immunotherapy relies upon specifically activating an immune response to distinct targets that are found within cancer lesions. Unfortunately, clinical efforts to date have been disappointing since not everyone is eligible (due, for example, to the lack of these targets) or only transient protective benefits are achieved. The major objective of our proposed studies is to develop a new immunotherapeutic approach that overcomes many current clinical limitations. Rather than directly killing tumor cells, we are attempting to discover “universal” targets that drive destructive immune responses against blood vessels, which allow tumor cells to grow and spread. Ultimately, we hypothesize that regardless of prior relapsed treatments, immunotherapy against tumor blood vessels will revert cancer growth and provide long-lasting protection against metastatic disease. Career Goals and Development: The Principal Investigator’s (PI’s) career goals are to (i) advance an independent career in cancer research and (ii) develop a novel translational research program in immunotherapy for colorectal cancer. Although the PI has significant experience in tumor immunology and developing immunotherapies for malignancies such as melanoma and kidney cancer, the PI has not yet expanded the scope of his work to colon cancer. This award will, therefore, provide the opportunity to develop an innovative research program in colon cancer where anti-vascular strategies (as outlined in the proposal) have not been applied. Overall, this funding mechanism will advance the PI’s career in the Peer Reviewed Cancer Research Program Topic Areas of colorectal cancer and immunotherapy. The PI will be mentored by a team of independent and established cancer scientists (typified by significant publications, patents, and funding history) who have collective research expertise in colon cancer, tumor angiogenesis, cancer therapeutics/immunotherapy, and cell signaling/epigenetics. Therefore, with a personalized development plan in place, the mentoring team will provide the necessary career and research guidance to ensure the PI achieves his career goals. Research Applicability: We expect that successful completion of this grant proposal will improve the field of cancer research and patient care by advancing (i) our basic understanding of the immune system’s role in interacting with blood vessels during colon cancer growth, (ii) the development of novel anti-blood vessel immunotherapeutic approaches, and (iii) our ability to seek larger grant support for clinical trial funding. Since these studies are in the earliest stages of development, we anticipate to demonstrate clinically relevant results within 2 years and clinically adopt our research findings for patient treatment within 5-10 years. We expect this new immunotherapeutic strategy will lead to breakthroughs in the ability to safely and effectively eliminate metastatic disease in treatment-naïve/previously treated patients with colon cancer. Additionally, since the blood vessel targets we are studying are conserved among cancer types, our work will also provide treatment solutions to individuals suffering non-colon cancer malignancies that require blood vessels to grow such as liver cancer and melanoma. Military Relevance: Colon cancer is a dangerous disease that is commonly diagnosed in young and middle-aged women and men. Currently, metastatic forms of colon cancer is a leading cause of death in the United States. The proposed research will, therefore, have a significant impact on the health and well-being of active duty Service members, military families, and Veteran popul
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810293
Entities
People
- Devin Lowe
Organizations
- Texas Tech University Health Sciences Center
- United States Army