Enhancing T-Cell Immunotherapy to Treat Pediatric Patients with Relapsed or Refractory Solid Tumors
Abstract
Scientific Objective/Rationale This proposal aims to optimize the use of T cells, a major component of the body’s immune system that fights virus infections and cancers, to treat solid tumors. Solid tumors account for one-third of patients diagnosed with cancer from birth to 19 years of age and is often fatal in patients with relapsed or treatment-resistant disease. Older patients or those with specific mutations are at particularly high risk. The failure of chemotherapy and radiation to cure these patients led us to explore novel strategies, based on the use of T cell products called tumor-associated antigen-specific T cells (TAA-T) that are expanded from patients’ blood to be specific for certain proteins on tumor cells. While initial studies show that this strategy is safe and well-tolerated for patients with solid tumors, solid tumors utilize many methods to suppress and evade the immune system. Additional strategies are needed to improve the function of T cells after infusion and product generation. In this application I am investigating how a patient’s tumor killing immune cells function and persist when administered after specific chemotherapy. In the lab, I am also evaluating if TAA-T that are generated from healthy donors matched to tumor cells (similar to what is done with bone marrow transplants) demonstrate killing of tumor without destroying the surrounding tissue. This would allow us to build a “TAA-T bank” of products that are ready to be used as soon as they are needed (known as “off the shelf”). Principal Investigator This research proposal supports my ultimate goal of becoming an independently funded physician scientist in the field of pediatric, adolescent, and young adult oncology. My particular focus on immunotherapy for relapsed or treatment-resistant cancers can be translated to a broad population of patients, including those with metastatic cancers, neuroblastoma, and pediatric brain tumors. I will initially gain laboratory experience and complete didactic training and will later focus on manuscript and grant preparation with the intent to open a clinical trial investigating our bank of “off the shelf” T cell therapy products. Dr. Catherine Bollard will provide guidance throughout the award period in the areas of T cell immunology, clinical trial design, clinical cellular banking, and grantsmanship/publication to ensure graduated independence toward my end-goal of becoming an independent physician-scientist. Impact on Cancer Research and Patient Care If successful, these studies will demonstrate that administering T cell therapy after receiving lympho-depleting chemotherapy is safe and feasible for patients with relapsed or treatment-resistant solid tumors. Successful completion of the second aim will establish a third-party TAA-T bank for “off the shelf” use in future clinical trials. These findings could extend T cell therapies to a broader group of patients with high-risk solid tumors and pave the way for the successful development of combination therapies to boost the activation of the body’s immune system to fight cancer. Ultimately, this proposal has the potential to improve the prognosis of pediatric cancer patients without subjecting them to increased side effects. Projected Timeline The first year of my award will entail collection of peripheral blood and tumor samples from patients and generation and characterization of TAA-T products from healthy donors, while didactics and attendance at conferences will enhance my foundation of knowledge. In the second year, I will continue immune studies, perform laboratory studies to investigate the tumor-killing ability of third-party TAA-T products, and develop strategies to improve patient care. Attendance at conferences and enrollment in didactic sessions will enhance my knowledge base during these 2 years. In the third and final year, I will focus on synthesis of data, manuscript preparation, leadership training, and initiation of
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110259
Entities
People
- Amy Hont
Organizations
- United States Army