Brain Disorders & Therapy

Oncolytic HSV-1 therapy for breast cancer meningeal metastases

International Conference on Neuro Oncology and Rehabilitation

July 21-22, 2016 Brisbane, Australia

Darshini Kuruppu

Massachusettes General Hospital, USA

Posters & Accepted Abstracts: Brain Disord Ther

Abstract:

Meningeal metastasis is a fatal complication of breast cancer that affects 5-8% of patients when cancer cells seed in the meninges. Their subsequent growth results in severe neurological complications involving the cranial nerves, cerebrum and spinal cord, limiting life expectancy to less than 4 months. Currently, there is no cure. Aggressive multimodal therapies such as radiation, intracerebrospinal fluid (CSF) and systemic chemotherapy are ineffective. Chemotherapy is often cleared rapidly from the CSF preventing access to cancer cells, while therapeutic doses are highly toxic. This highlights the urgent need for new therapy. Oncolytic Herpes Simplex Virus type 1 (HSV-1) was investigated in this regard. Oncolytic viral therapy is the destruction of cancer cells by replicating virus. It is based on the model of multiple cycles of lytic virus replication in cancer cells until the cancer is destroyed. This investigation was conducted in a murine model of meningeal metastases which has been fully characterized by in vivo molecular imaging, histology and external neurological symptoms and shown to mimic human disease pathology. Based on out results, oncolytic HSV-1 inhibits tumor growth primarily in the base of the brain and spinal cord. The onset of neurological symptoms (bradykinesia, ataxia, anorexia, and paralysis) that accompany a heavy tumor burden in the base of the brain were delayed. Replicating virus is identified in tumors. Treatment at the early phase of tumor growth had a higher response rate compared to that at the late phase of tumor growth. Our investigations show that treatment of meningeal metastases with oncolytic HSV-1 at the early growth phase can inhibit life threatening disease progression. As such oncolytic HSV-1 holds promise as a potential therapy for breast cancer meningeal metastases that can be translated to the clinic.

Biography :

Email: DKURUPPU@mgh.harvard.edu