MICaB Graduate Program
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Thomas S. Griffith, Ph.D.
Washington University, Ph.D., 1996
Tumor immunology, apoptosis
The research in my laboratory studies the therapeutic potential of apoptotic cell death in the treatment of cancer. The tumor necrosis family member, TRAIL/Apo-2 ligand, is a potent inducer of tumor cell apoptosis, but is non-toxic against normal cell and tissues, suggesting that TRAIL might be administered as an antitumor therapeutic without the side effects seen with other TNF family members, namely TNF and Fas ligand, and traditional chemotherapeutics.
Employment of various gene delivery systems, such as non-replicative viral vectors, is making it possible to administer genes directly into tumors sites in situ. Using this technology, a recombinant, replication-deficient adenoviral vector encoding the full-length TRAIL cDNA (Ad-TRAIL) was developed in the laboratory as a way to induce tumor cell death. Current experiments are investigating the ability of Ad-TRAIL to activate systemic antitumor immunity.
Additional studies are investigating the ability of apoptotic cells to influence the immune response. For these studies, we use a number of experimental model of tolerance as well as an experimental model of sepsis.
Selected Recent Publications:
- EL Brincks, P Gurung, RA Langlois, EA Hemann, KL Legge, TS Griffith. 2011. The magnitude of the T cell response to a clinically-significant dose of influenza virus is regulated by TRAIL. Journal of Immunology. In press.
- P Gurung, D Rai, SA Condotta, JC Babcock, VP Badovinac, TS Griffith. 2011. Immune unresponsiveness to secondary heterologous bacterial infection after sepsis induction is TRAIL-dependent. Journal of Immunology 187: 2148.
- LA Norian, BR James, and TS Griffith. 2011. Advances in viral vector-based TRAIL gene therapy for cancer. Cancers 3: 603.
- P Gurung, TA Kucaba, SP Schoenberger, TA Ferguson, TS Griffith. 2010. TRAIL-expressing CD8+ T cells mediate tolerance following soluble peptide-induced peripheral T cell deletion. Journal of Leukocyte Biology 88: 1217.
- P Gurung, TA Kucaba, TA Ferguson, TS Griffith. 2009. Activation-induced CD154 expression abrogates tolerance induced by apoptotic cells. Journal of Immunology 183: 6114.
- EL Brincks, A Katewa, TA Kucaba, TS Griffith, KL Legge. 2008. CD8 T cells utilize TNF-related apoptosis-inducing ligand (TRAIL) to control influenza virus infection. Journal of Immunology 181: 4918.
- RL VanOosten and TS Griffith. 2007. Activation of tumor-specific CD8+ T cells after intratumoral Ad5-TRAIL/CpG ODN combination therapy. Cancer Research 67: 11980.