Dr. Michael A. Curran
The University of Texas MD Anderson Cancer Center
Department of Immunology
- Tumor immunology
- T-cell activation
- Myeloid derived suppressor cells
- Combination therapies
- Cancer vaccines
Previously, I discovered a novel T-cell polarity dependent on high expression of the transcription factor Eomesodermin. These cells are the primary mediators of melanoma tumor rejection following treatment with 4-1BB agonist antibody. My lab seeks to understand the origin and biologic significance of these cells, as well as to use transgenic T-cells in vitro polarized to this highly cytotoxic phenotype for T-cell adoptive transfer therapy.
Also, we have discovered a novel synergy between the destruction of hypoxic regions of tumors and the ability to mobilize peripheral anti-tumor T-cell responses using antibodies which modulate T-cell co-stimulation. We are investigating the pre-clinical activity and molecular mechanism of action of this therapy in pre-clinical models of prostate cancer and pancreatic adenocarcinoma, as well as preparing a phase I clinical trial to test this combination in patients.
Student projects begin from a clear and testable hypothesis which falls within the lab's tumor immunology focus. Projects generally involve testing the therapeutic efficacy of a given approach in murine tumor models, formulating in vivo experiments in reporter and/or knockout mice to reveal underlying biologic mechanisms, and isolating tumor infiltrating cells. Relevant lymphocytes or myeloid cells may be directly analyzed using flow cytometry, or their relevant effector functions may be measured using a variety of immunologic assays including Elispot and in vitro cytotoxicity. Whenever possible, discoveries in murine tumor models are validated through analysis of patient samples from relevant clinical trials.
Curran, M.A.*, Jenq, R.R.*, Goldberg, G., Allison, J.P. and van den Brink, M.R. Repertoire enhancement with adoptively transferred female lymphocytes Controls the Growth of Pre-Implanted Murine Prostate Cancer. PLoS-ONE 2012; 7(4).
Curran, M.A., Kim, M.J., Montalvo, W., Al-Shamkhani, A. and Allison, J.P. Combination CTLA-4 blockade and 4-1BB activation enhances tumor rejection by increasing T-cell infiltration, proliferation, and cytokine production. PLoS ONE 2011; 6(4).
Curran, M.A., Montalvo, W., Yagita, H. and Allison, J.P. Combination PD-1 and CTLA-4 pathway blockade synergistically expands infiltrating T-cells and reduces regulatory T and myeloid cells in the B16 melanoma microenvironment. PNAS 2010; 107(9):4275-4280.
Curran, M.A. and Allison, J.P. Tumor Vaccines Expressing Flt3-Ligand Synergize with CTLA-4 Blockade to Reject Pre-implanted Tumors. Cancer Research 2009; 69(19):7747-55