Mutation-Targeted Immunotherapy for the Treatment of Rare Cancers
Abstract
Cancer is the second leading cause of death in the United States (U.S.), accounting for more than 600,000 deaths each year. Approximately 20% of all cancers diagnosed in the U.S. are classified as a rare cancer. As is the case with many cancers, developing effective treatments for rare cancers, which individually affect fewer than 6 out of 100,000 people, has been exceptionally challenging. However, in addition to the technical challenges facing the development of these therapies, rare cancer therapies also face challenges in clinical translation. With a total U.S. market size below 20,000 individuals annually, any new therapy developed must offer a compelling value proposition (e.g., substantial life extension and/or reduced side effects) to motivate commercial interest and clinical trials. Further, once clinical trials begin, there must be a sufficient number of patients enrolled to yield statistically meaningful results. Unfortunately, many clinical trials in the past—particularly those for rare cancers—have been stymied by insufficient patient recruitment. Therefore, an ideal therapy for rare cancers would be broadly effective for multiple types and stages of rare cancers to provide both ample motivation for commercialization and basket trials with sufficient enrollment for clinical trial advancement. In this Concept Award, we will establish proof-of-concept for a therapeutic platform that kills cancer cells based on the direct recognition of cancerous mutations to the genome that are inherent to all rare cancers, which makes it well-aligned with the Fiscal Year 2020 Rare Cancer Research Program Therapy Focus Area, which seeks to identify novel therapeutic strategies. The primary problem facing the development of safe and effective cancer chemotherapeutics is the inability to selectively kill tumor cells without damaging healthy tissues. This lack of specificity limits the doses that can be safely administered, often resulting in an inadequate therapeutic effect. Rather than using a generic approach to treat a disease that varies greatly between cancers, between patients, and even within a patient’s tumor, we will produce personalized formulations that target cancer cells based on mutations unique to each individual’s disease. By leveraging the specificity of clustered regularly interspaced short palindromic repeats (CRISPR), we will selectively edit and kill tumor cells without damaging surrounding normal tissue. We will demonstrate the specificity and efficacy of this approach in both vulvar squamous cell carcinoma and primary clinical vulvar cancer samples. In addition to developing a new approach with potential clinical implications, this research will also establish a methodology for studying therapeutic efficacy in primary patient samples, increasing the likelihood that early successes translate to humans—a persistent problem when transitioning cancer therapies from animal to human models. The research conducted under this one-year award will directly impact the 6,120 women diagnosed each year with vulvar cancer and open up new treatment opportunities for more than 350,000 individuals diagnosed with rare cancers each year in the United States. This research also has obvious potential implications for other forms of cancer as well, because it targets genomic mutations that are inherent to all cancers. We expect that the largest potential impact will be on individuals diagnosed with advanced-stage cancer. While there are effective treatments for some cancers when diagnosed at an early stage, treatments for advanced metastatic disease are often not very effective. This therapy has the potential to be locally or systemically delivered to destroy both the primary tumor as well as metastases, which cause 90% of all cancer deaths. In addition to potentially proving more effective than existing treatments, the highly specific nature of this approach is also expected to dramatically reduce damage to healthy tissues, whi
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110968
Entities
People
- Kevin Mchugh
Organizations
- Rice University
- United States Army