Samuel Rabkin, Ph.D.
Neurosurgery, Mass General Research Institute
Thomas A. Pappas Professor of Neurosciences
Neurosurgery, Harvard Medical School
Harvard Stem Cell Institute
Department of Microbiology, Harvard Medical School
|MSc Hebrew University of Jerusalem 1978|
|PhD University of Chicago 1983|
Research in my laboratory focuses on the use of herpes simplex virus (HSV) vectors for cancer therapy and gene delivery in the nervous system, with the long-term goal being the therapeutic application of these vectors to patients. Oncolytic HSV is genetically-engineered/mutated to selectively replicate in cancer cells, but not normal cells, and be non-pathogenic. In addition, oncolytic HSV can also be transcriptionally-targeted, where viral replication and associated cytotoxicity are driven by cell-specific promoters/enhancers. Finally, oncolytic HSV can be 'armed' to express therapeutic transgenes locally in the tumor. New virus constructs are tested in various in vivo tumor models for efficacy and mechanism of action, and their safety assessed. The combination of oncolytic HSV with other cancer treatment modalities, such as chemotherapy and molecularly targeted drugs, to enhance efficacy is being evaluated.
Our studies concentrate on glioblastoma and tumors arising in neurofibromatosis patients, such as meningioma and malignant peripheral nerve sheath tumors, as well as other solid tumors like prostate cancer. The tumor models include; human xenografts in nude mice or syngeneic mouse tumor implants (subcutaneous, intracranial, orthotopic) and spontaneous tumors in transgenic mice.
We are particularly interested in glioblastoma stem-like cells, and other cancer stem cells, in order to understand tumor biology and as representative models for experimental therapeutics.
In addition to direct cytotoxic activity, oncolytic HSV induces specific anti-tumor immune responses, in essence acting as an in situ cancer vaccine. To enhance the anti-tumor immune responses we are arming the viruses with immune-modulatory genes and/or combining them with pharmacological immune modulators such as immune checkpoint inhibitors.
Current Research Areas:
- Development of new oncolytic HSVs
- Immunotherapy for brain tumors
- Characterization of glioblastoma stem-like cells
- Combination therapies with oncolytic HSV and drugs inhibiting DNA damage responses and oncogene pathways.