Therapeutic Targeting of Immune Dysfunction in Langerhans Cell Histiocytosis
Abstract
Langerhans cell histiocytosis (LCH), the most common histiocytic disorder, is a rare form of cancer that occurs mostly in children. The incidence of LCH is 3 to 5 cases per million children, like that observed in Hodgkin Lymphoma or acute myeloid leukemia. However, patients with LCH have benefited far less from research funding and attention than other childhood cancers – likely due to incomplete understanding of the disease. Research by us and others over the last decade has contributed to a better understanding of (a) how the genetic information in LCH patients is different compared to healthy children, and (b) how immune cells in LCH patients misbehave to facilitate progression of the disease. Identification of these molecular footprints have now allowed us the opportunity to start testing novel therapeutic strategies targeting both the genetic changes and the misbehaving immune cells. However, these alternative therapies initially need to be tested in pre-clinical settings to define the right combination, understand efficacy, toxicity, and adverse side effects before being moved forward to phase 0 and phase 1 clinical trials. Hence, the objective of the proposed research is to both understand how altered genetic composition affects resistance/susceptibility to current treatments and how those could be targeted to obtain a better outcome. The Principal Investigators (PIs) long-term goal as a scientist is to enable pediatric patients to receive targeted immunotherapies as standard of care across childrens cancer centers, a vision she plans to achieve through highly innovative and collaborative research, and successfully developing strategies to redirect or reinvigorate human cytotoxic T cells for targeted killing of cancers. The Peer Reviewed Cancer Research Program Career Development Award will provide the PI a wonderful opportunity to develop her skills as she continues to build her academic research career in translational pediatric hematology-oncology. Successful completion of the proposed research will provide critical data, as well as lay the platform to obtain further research support during early phase of her independent research career as a cancer biologist. Additionally, in a disease that has been historically restricted to incremental clinical advances the proposed research will thus provide a foundation for the next generation of LCH treatment strategies with a personalized approach and laying the framework for other similar myeloid cancers.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910167
Entities
People
- Rikhia Chaudhury Chakraborty
Organizations
- Baylor College of Medicine
- United States Army