GENE THERAPY FOR IMMUNO-ONCOLOGY APPLICATIONS
Researchers at the Chan Zuckerberg Biohub and UCSF have developed viral gene therapy delivery systems for therapeutic immuno-oncology applications.
Glioblastoma is the most common and deadliest primary malignant brain cancer with an overall median survival of 14.6 months. Therapies currently in use, and in development, are limited in safety, efficacy or applicability. Recent advances in immuno-oncology therapies, which harness the power of the immune system to help treat cancer, have resulted in improved patient outcomes in several tumor types. For example, interferons (IFNs) function to stimulate innate immunity and have a variety of direct and indirect anti-tumor functions. Although IFN therapies can induce antitumor responses, chronic stimulation of IFN signaling by systemic administration can cause secondary toxicities.
Stage of Research
The inventors have developed a targeted viral gene delivery system for interferon-based treatment of cancers, such as glioblastoma. Specifically, they developed recombinant adeno-associated viruses (rAAVs) encoding IFN polypeptides. rAAVs are generated and applied to tumor cells to stimulate IFN-mediated signaling and antitumor responses. The inventors demonstrate the cytostatic effects of human IFNß therapy in glioblastoma tumor spheroid cultures. Furthermore, they show significant increases in overall survival in several orthotopic mouse models of glioblastoma after local rAAV application.
Applications
- In vivo immunotherapy treatment of glioblastoma and other solid tumors
- Targeted delivery and expression of interferon polypeptides
Advantages
- Targeted local application by convection enhanced delivery (CED), bypassing blood brain barrier limitations
- CED is compatible with tracer administration and often guided by magnetic resonance imaging (MRI)
- rAAVs are naturally replication-deficient and can transduce nearly every mammalian cell type, including quiescent tissues
- Therapeutic application of types I and II IFNs
- Combinatorial application of IFNs with bi- and tri-cistronic viral vector delivery systems
Stage of Development
Research – in vitro
Publications
N/A
Related Web Links
http://derisilab.ucsf.edu/
Keywords
Glioblastoma, gene therapy, recombinant adenoviral-associated virus (rAAV), Interferon (IFN), convection enhanced delivery, immuno-oncology
Technology Reference
Chan Zuckerberg CZB-128F, UCSF SF2019-216
