The tumor microenvironment (TME) is a complex system containing multiple cell types and cytokines that control cancer cell growth and promote cancer immune evasion. In cases of glioblastoma (GBM), the most common and deadliest brain cancer in adults, the TME plays a particularly prominent role in disease progression and poor response to therapy. Despite aggressive multimodal treatment options, GBM remains incurable, with a median survival time after diagnosis of only 15-16 months. And despite recent the recent success of immunotherapy in treating other types of cancer, immunotherapy interventions in brain cancer are largely ineffective. Currently, there are no FDA-approved immune therapies for this aggressive and deadly type of cancer.
Description
Pitt researchers have discovered three novel immunomodulators of the TME that form protein binding complexes capable of controlling tumor-associated macrophages, which are the major components of the glioblastoma TME. This discovery enabled the design of a new peptide that interacts with the recently discovered immunomodulators to modify the TME to enhance antitumor immune response. Animal experiments revealed that this treatment produced an increase of T cell infiltration and expression of immune checkpoint inhibitors, suggesting the potential of the newly developed peptide to overcome GBM resistance to immunotherapy and synergize with immune checkpoint blockade therapy by combining with other FDA-approved drugs, sch as nivolumab or pembrolizumab. This new peptide could give rise to a novel class of drug candidates, including small molecule compounds and therapeutic antibodies, for treating glioblastoma and other types of cancer.
Applications
· Developing biomarker panels to guide cancer immunotherapy
· Developing drug candidates to treat glioblastoma
· Developing new combination therapy protocols to make existing but previously ineffective therapies, such as immune checkpoint blockade therapy, viable and potent options
· Developing drugs to treat other brain tumors and other types of cancer
Advantages
· Biomarker-guided cancer therapy
· Entirely novel mechanism for treating GBM
· Improves TME response to immune checkpoint therapy, enabling the use of synergistic combination therapies
Invention Readiness
In vivo data
IP Status
https://patents.google.com/patent/US20240156901A1
