The poor prognosis of glioblastoma multiforme even after resection, chemotherapy and radiation has led to an interest in immunotherapy which necessitates consideration of the blood-brain barrier (BBB). Attenuated rabies viruses (RABV) induce BBB modifications that allow immune effectors to reach the CNS without immunopathology. We have shown that induction of a CNS response to an attenuated RABV can significantly prolong the survival of mice bearing intracranial GL261 tumors. This extended survival is associated with delayed tumor growth and an increase in mRNA levels of T and B cell markers and IFN-γ in CNS tissue. However it is not yet known whether the delayed tumor growth is a result of non antigen-specific effects of the antiviral response or due to BBB modifications that facilitate contact between the tumor cells and immune system. To provide a more selective target for the immune response, we have engineered a recombinant RABV to express human survivin. Survivin, an inhibitor of apoptosis protein (IAP), is preferentially expressed at high levels in certain types of cancer cells including gliomas and has been successfully used as a target in GL261 immunotherapies. The expression of survivin by RABV is expected to promote the delivery of tumor-reactive immune effectors into CNS tissues.
- Copyright © 2013 by The American Association of Immunologists, Inc.