Faculty

Dawn E Post, Ph.D. Assistant Professor, Neurosurgery 4117 Institute For Human Performance Upstate Medical University 750 East Adams Street Syracuse, NY 13210 (315) 464-9370

Research Program and Department Affiliations

Research Interests

Research Abstract

Oncolytic viruses for brain tumor therapy

Oncolytic virotherapy is an emerging anti-cancer treatment using replicative lytic viruses, such as Adenovirus (Ad) and Herpes Simplex Virus-1 (HSV). Oncolytic Ad and HSV are biological anti-tumor agents that offer several advantages including an intrinsic ability to kill infected host cells at the completion of the virus replicative cycle and the capacity to deliver therapeutic transgenes. A major focus of the lab is to develop oncolytic Ads and HSVs for brain tumor therapy and evaluate their efficacy in cell culture and in vivo using preclinical brain tumor models.

We exploit the presence of hypoxia, low oxygen conditions, in tumors compared to normal tissue as an avenue for the development of targeted oncolytic Ads and HSVs. We are currently evaluating the therapeutic potential of an oncolytic Ad that selectively replicates under hypoxic conditions and is armed with the interleukin-4 therapeutic transgene (HYPR-Ad-IL4, Cancer Research, 2007). The anti-tumorigenic IL-4 cytokine was chosen because it exhibits multimodal anti-tumor activity including induction of a host anti-tumor immune response and inhibition of tumor angiogenesis. HYPR-Ad-IL4 selectively kills hypoxic tumor cells via the viral cytolytic replication cycle and has potent antitumor activity resulting in long-term tumor regressions. Now that we have established the therapeutic efficacy of HYPR-Ad-IL4, it will be important to conduct detailed mechanistic, safety, and toxicity studies of this virus towards clinical translation.

These promising results support the future development of hypoxia-dependent oncolytic viruses as a therapy for a broad range of tumor types that develop hypoxia. We are exploring several strategies to enhance the potency of HYPR-Ad-IL4 and are also designing HYPR-Ads with other therapeutic transgenes. In addition, the lab received an NIH grant to construct and evaluate the therapeutic efficacy of an oncolytic HSV that selectively replicates in hypoxic tumor cells (HYPR-HSV) and a modified HYPR-HSV that delivers therapeutic transgenes. Our goal is the translation of these laboratory studies into Clinical Trial testing for the purpose of improving the quality of life and survival of brain tumor patients.

Selected References:

1. Post, D.E., Sandberg, E., Kyle, M.M., Devi, N.S., Brat, D.J., Xu, Z., Tighiouart, M., and Van Meir, E.G. (2007) Targeted cancer-gene therapy using a HIF-dependent oncolytic adenovirus armed with interleukin-4. Cancer Research, in press.
2. Post, D.E., Devi, N.S., Li, Z., Zhang, Z., Brat, D.J., Kaur, B., Nicholson, A., Olson, J.J., Zhang, Z., and Van Meir, E.G. (2004) Cancer therapy with a replicating oncolytic adenovirus targeting the hypoxic microenvironment of tumors. Clin. Cancer Res. 10, 8603-12.
3. Post, D.E. and Van Meir, E.G.(2003) A novel hypoxia-inducible factor (HIF) activated oncolytic adenovirus for cancer therapy. Oncogene 22, 2065-72.
4. Post, D.E. and Van Meir, E.G. (2001) Generation of bidirectional hypoxia/HIF-responsive expression vectors to target gene expression to hypoxic cells. Gene Therapy 8, 1801-07.
5. Post, D.E., Shim, H., Toussaint-Smith, E., and Van Meir, E.G. (2005) Cancer scene investigation: how a cold virus became a cancer killer. Future Oncology 1, 247-258, invited review.
6. Chu R., Post D.E., Khuri F. andVan Meir E.G. (2004) Use of replicative oncolytic adenoviruses in combination therapy for cancer. Clin. Cancer Res. 52, 5299-312.
7. Post, D.E., Fulci, G., Chiocca, E.A., and Van Meir, E.G. (2004) Replicative oncolytic herpes simplex viruses in combination cancer therapies. Current Gene Therapy 4, 41-51.

Publications - link to PubMed

This profile was last updated on 09/29/2008

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