Restricted Research - Award List, Note/Discussion Page
Fiscal Year: 2023
1893 The University of Texas at El Paso (143781)
Principal Investigator: Vines,Charlotte M
Total Amount of Contract, Award, or Gift (Annual before 2011): $ 153,500
Exceeds $250,000 (Is it flagged?): No
Start and End Dates: 12/15/22 - 11/30/24
Restricted Research: YES
Academic Discipline: Biological Sciences
Department, Center, School, or Institute: Biological Sciences
Title of Contract, Award, or Gift: R03: Development of a Mouse Model to Study Targeted Therapy to Prevent CNS Invasion by Pediatric T-ALL
Name of Granting or Contracting Agency/Entity:
NIH - NATIONAL CANCER INSTITUTE
CFDA Link: HHS
93.396
Program Title:
Cancer Biology Research
CFDA Linked: Cancer Biology Research
Note:
Acute lymphoblastic leukemia (ALL) is the most common leukemia in children, and there is lower survival of Hispanics for ALL compared to Non-Hispanic Whites. Children within our El Paso region have a lower overall survival than other regions of the state. Unfortunately, in 15-20% of these children, the cancer invades the Central Nervous System (CNS) requiring that the children undergo toxic intrathecal chemotherapies and cranial irradiation; both treatments often lead to morbid life-long side effects. In a mouse model of TALL, activation of CC chemokine receptor 7 (CCR7) by CCL19 plays a role in trafficking T-ALL into the CNS. It is well established that CCR7 is an important chemokine receptor in the migration of naïve T-cells to lymph nodes and we hypothesize that similar mechanisms contribute to T-ALL migration into the brain in response to CNS-expressed CCL19. The long-term goal of our project is to define novel platforms to treat T-ALL via blocking CCR7 that we expect will prevent T-ALL cells from entering the CNS, and to determine if any or all T-ALL cells already in the CNS exit via the cranial lymphatic system. If successful, pediatric T-ALL survivors will not have to endure harmful chemotherapy and radiation treatments and live healthier more productive lives. To reach our goal, we will establish a mouse model of pediatric T-ALL, in which we can test the role of CCR7 in CNS invasion/persistence, to test our hypothesis. In addition, since cancer invasion is typically associated with immune cell infiltration, we will study these immune cells by histological sectioning, marker staining and multi-parametric flow cytometry to analyze the composition of individual immune cells. Finally, since CCR7 and or CCL19 mutations can drive CCR7 activation, we will sequence cDNA prepared from patient T-ALL samples to assess this possibility.
Discussion: No discussion notes