Huntsman Cancer Research Institute
In 2023, the Ty Louis Campbell (TLC) Foundation supported the project “Leveraging Super-Multi-Parameter Fluorescence Activated Cell Sorting Analysis to Obtain a Comprehensive Understanding of the Immune System Consequences of Irradiation and Anti-CD47 Treatments in Group 3 Medulloblastoma” with a $100,000 donation.
Medulloblastoma (MB) is the most common malignant primary brain tumor in children, and the Group 3 subtype of MB is the deadliest type, with only 25% long-term survival. TLC was one of the first nonprofits to support Dr. Samuel Cheshier’s immunotherapy research since 2013, which recently proved that a therapy called “anti-CD47” can make immune system cells called “macrophages” literally eat tumor cells via a process called phagocytosis.
Furthermore, Cheshier’s team showed that anti-CD47 had potent activity against human group 3 MB cells while causing no harm to normal brain cells. We helped to fund the Phase 1 clinical trial with anti-CD47 in children with recurrent brain tumors, including group 3 MB, that is currently underway (see clinicaltrials.gov).
In anticipation of the next stage of anti-CD47 clinical trials, Dr. Cheshier is now conducting experiments to determine therapies that can further enhance the effectiveness of anti-CD47. His team is exploring how irradiation can be most effectively combined with anti-CD47. Cheshier has already determined that irradiation can greatly enhance macrophage eating of group 3 medulloblastoma cells by anti-CD47. However, irradiation can enhance and inhibit the immune system’s ability to fight cancers, and irradiation’s overall effect on the immune system, in terms of the anti-CD47 system, is entirely unknown.
This project leverages sophisticated research instruments to examine how group 3 medulloblastoma modulates the signals they send to the immune system in response to irradiation, anti-CD47, and when we combine the two treatments. From this data, we will understand how the tumor modulates each branch of the immune system, which will lead to data bio-signatures that indicate whether the immune system responds to the treatments and if the treatment is effective.
Furthermore, we will learn how to better combine many other immune therapies with irradiation and anti-CD47. This data will improve our understanding of the immunological consequences of each treatment and will directly inform future clinical trials, which we hope will improve treatment outcomes for children with group 3 medulloblastoma among other tumor types.
PHOTO CREDIT: HUNTSMAN CANCER INSTITUTE
