Title: Immunosignature strategy for development of clinical biomarkers and identification of new drug target candidates for pediatric brain cancer
Investigators: Bob Carter, Stephen Johnston, Robert Wechsler-Reya
Grantees: University of California San Diego, Arizona State University, Sanford-Burnham Prebys Medical Discovery Institute
Immunosignatures are a new, state-of-the-art technology with the potential to make early brain cancer detection a reality. This new technology works by looking at how antibody signals in the blood change when the immune system – the body’s natural defense against invaders like cancer – detects a brain tumor. Upon sensing a tumor, the immune system tries to mount an attack using antibodies that recognize unique molecular textures on the surfaces of the tumor cells. Just a single drop of blood contains enough of these tumor-recognizing antibodies to reveal specific, accurate information about the particular characteristics of a tumor.
Simple blood tests analyzing the patterns of these tumor-recognizing antibodies, also known as immunosignatures, have already been shown by Dr. Johnston's lab in the BioDesign Institute at Arizona State to recognize different types of adult brain cancer. Based on the success of such blood tests in adults, ABC2 in 2015 brought leading doctors and scientists at the University of California San Diego and the Sanford-Burnham Prebys Medical Discovery Institute together with the Johnston group at Arizona State to apply this powerful immunosignature technology to pediatric medulloblastoma.
The goal of the collaboration funded by ABC2 is to develop immunosignature-based blood tests for detecting, classifying, and monitoring pediatric medulloblastoma over time. As in adults, the idea is to identify different patterns of tumor-recognizing antibodies in the blood that indicate the presence/absence of medulloblastoma and differentiate between tumors of different types in children. Once such patterns are identified, they will be examined in both established and newly improved laboratory models to verify their accuracy, determine their relationship to disease progression and therapeutic response, and inform the search for new medulloblastoma therapy targets.
If this work is successful, it could lead to blood tests that allow early detection, accurate diagnosis, and straightforward monitoring of pediatric medulloblastoma. Together with identifying potential new targets for therapy, these advances could significantly improve childhood brain cancer treatment.
Antibodies: The immune system produces and secretes into the bloodstream specialized proteins called antibodies that are constantly on the lookout for foreign invaders like viruses, bacteria—and cancer cells. Antibodies recognize these invaders by sticking to unique molecular textures that are present on the surfaces of foreign invaders but not healthy cells in the body. Under most circumstances, these antibodies then trigger a broad range of attack mechanisms that neutralize and clear the body of the foreign invaders. However, cancers somehow prevent the immune system from mounting its full attack, even when tumor-recognizing antibodies do detect the presence of cancer cells.