Perturbomics Identification of Critical Genetic Targets in NK Cells for Breast Cancer Therapy
Abstract
Breast cancer is the most common cancer and the second leading cause of cancer death in women. Although standard of care have good prognosis, in general, late-stage and metastatic breast cancers are still lethal. Therefore, new and better treatment options are unmet urgent needs for breast cancer patients. Cell therapy is a powerful means of cancer treatment; however, currently existing cell therapies face major challenges in solid tumors including breast cancer. Natural killer (NK) cell is an innate immune cell type that serves at the first level of defense against pathogens and cancer. The development of genetically engineered chimeric antigen receptor (CAR) cells has shown great therapeutic potential in NK cells. However, despite all these efforts, there is no approved CAR-NK therapy to date. Current forms of NK cell-based immunotherapy candidates face a number of obstacles. NK cells encode the same collection of about 20,000 protein coding genes in their genome, many of which might play critical roles in regulating or limiting the antitumor function of NK cells. We hypothesize that systems approaches can identify critical regulators of NK cells to enhance NK-based cell therapy against breast cancer. Our goal is to use unbiased in vivo screens and single-cell sequencing to produce maps of genetic regulators of tumor-infiltrating NK cells, then perform gene editing of these regulators to enhance the function and antitumor efficacy of CAR-NKs against breast cancer. This project addresses the fiscal year 2022 (FY22) Breast Cancer Research Program (BCRP) overarching challenge Revolutionize treatment regimens by replacing them with ones that are more effective, less toxic, and impact survival. This project’s research output will help late-stage breast cancer patients, especially those with cancer antigen positive population, such as HER2 positive or MUC1 positive. This is a 3-year project. The direct outcome of this project will provide fundamental new knowledge on natural killer cells in breast cancer, plus new cell therapy candidates for breast cancer treatment. The new cell therapy candidates can progress to further development and translational studies shortly after the completion of this project to approach clinical stage. These novel cell therapy candidates initially developed here, if successfully developed into clinical products in future years, will provide new treatments for late-stage breast cancer patients who are often out of options. This project is directly relevant to the health and well-being of Service Members, Veterans, their family members, and all people impacted by breast cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310472
Entities
People
- Sidi Chen
Organizations
- United States Army
- Yale University