Research Interests:
Dr. Powell’s laboratory is actively developing immunotherapeutic strategies, including experimental cell-based therapeutics, for the treatment of ovarian cancer.

Cell-based Immunotherapy
Adoptive transfer of autologous tumor-reactive T cells after host lymphodepletion represents an important advance in cancer immunotherapy. Nearly 50% of patients with refractory metastatic melanoma respond to adoptive T cell immunotherapy however its successful use for other solid tumor types has been limited. Our objective is to develop and test the feasibility of adoptive cellular therapy for the treatment of patients with ovarian cancer. To provide the basic research infrastructure for a continued, collaborative translational effort, our goals include the generation and characterization of highly avid, tumor-reactive T cell products for autologous patient transfer, development and optimization of ex vivo conditions to bolster the activity of the transferred cell population, and development of GMP-grade tumor-reactive T cell products in the Clinical Cell and Vaccine Production Facility for patient infusion. Since the presence of tumor-infiltrating lymphocytes (TILs) in ovarian cancers positively correlates with improved survival, we hypothesize that TIL represent a tumor-reactive T cell population with the potential for use in the immunotherapeutic treatment of ovarian cancer.

Genetically-modified Cell Therapy
Recent clinical trials have demonstrated the feasibility and capacity of genetically modified T cells, which express exogenous tumor antigen-specific T cell receptors (TCRs), to mediate objective cancer regression. An effort exists to identify, isolate and clone the genes encoding TCRs which confer high functional avidity to non-reactive T cells for potential use in future gene therapy trials for ovarian cancer. Additionally, modification of T cells to express genes encoding chimeric immune receptors capable of recognizing in tact cancer cell- or tumor vasculature-specific surface proteins will be investigated.

Cancer Vaccination
Successful cancer vaccination depends on the generation in vivo of sufficient numbers of tumor antigen-specific T cells of appropriate phenotype and function that are capable of homing to the site of disease and eradicating tumor. Cancer vaccines will also be instrumental in potentiating the in vivo effector function of tumor-specific T cells following their administration in adoptive immunotherapy trials. Ongoing efforts to improve the efficacy of current cancer vaccines include the use of cell-based vaccines, such as dendritic cells or modified tumor cells, Toll-like receptor agonists, immunomodulatory cytokines or antibodies and regulatory T cell-depleting regimens.

Recent publications
Palmer, D.C., Chan, C-C., Gattinoni, L. Wrzesinski, C., Paulos, C.M., Hinrichs, C.S., Powell Jr., D.J.,  Klebanoff, C.A., Finkelstein, S.E., Fariss, R.N., Yu, Z., Nussenblatt, R.B., Rosenberg, S.A. and Restifo, N.P. “Shared antigen-specific CD8+ T cells in ocular and tumor immunity following reversal of ignorance” PNAS. published online June 3, 2008, 10.1073/pnas.0710929105.

Powell Jr., D.J., Attia, P., Ghetie, V., Schindler, J., Vitetta, E.S. and Rosenberg S.A. “Partial reduction of human FOXP3+ CD4 T cells in vivo following CD25-directed recombinant immunotoxin administration” J Immunother. 31(2): 189-198, Feb/March 2008.

Powell Jr., D.J., Felipe-Silva, A., Merino M.J., Ahmadzadeh, M., Allen, T., Levy, C., White, D.E., Mavroukakis, S., Kreitman, R.J., Rosenberg, S.A. and Pastan, I. “Administration of a CD25-directed immunotoxin, LMB-2, to patients with metastatic melanoma induces a selective, partial reduction in regulatory T cells in vivo” J Immunol. 179(7):4919-28, Oct 2007.

Borbulevych, O.Y., Insaidoo, F.K., Baxter, T.K., Powell Jr., D.J., Johnson, L.A., Restifo, N.P. and Baker, B.M. “Structures of MART-126/27-35 peptide/HLA-A2 complexes reveal a remarkable disconnect between antigen structural homology and T cell recognition” J Mol Biol. 372(5):1123-36, Oct 2007.

Powell Jr., D.J., de Vries, C., Allen, T., Ahmadzadeh, M. and Rosenberg, S.A. “Inability to mediate prolonged reduction of regulatory T cells following transfer of autologous CD25-depleted PBMC and interleukin-2 after lymphodepleting chemotherapy” J Immunother. 30(4):438-47, May-Jun 2007.

Shen, X., Zhou, J., Hathcock, K.S., Robbins, P.F., Powell Jr., D.J., Rosenberg, S.A., and Hodes, R.J. “The role of telomere length in adoptive immunotherapy: Tumor infiltrating lymphocytes that persist following adoptive transfer fail to up-regulate telomerase in vivo and undergo telomere loss.” J Immunother. 30(1):123-9, Jan 2007.

Powell Jr., D.J., Dudley, M.E., Hogan, K.A., Wunderlich, J., and Rosenberg, S.A. “Adoptive Transfer of Vaccine-Induced PBMC to Patients with Metastatic Melanoma following Lymphodepletion” J Immunol. 177(9):6527-6539, Nov 2006.

Johnson, L.A., Heemskerk, B., Powell Jr., D.J., Cohen, C.J., Morgan, R.A., Dudley, M.E., Robbins, P.F., and Rosenberg, S.A. “Gene transfer of tumor-reactive T-cell receptors confers both high avidity and tumor-reactivity to non-reactive PBMC and TIL” J Immunol. 177(9): 6548-6559, Nov 2006.

Gattinoni, L.*, Powell Jr., D.J.*, Rosenberg, S.A. and Restifo, N.P. “Adoptive immunotherapy for cancer: Building on success.” Nat Rev Immunol. 6(5):383-93, May 2006. * Authors contributed equally

Attia, P., Powell Jr., D.J., Maker, A.V., Kreitman, R.J., Pastan, I. and Rosenberg, S.A. “Selective elimination of human regulatory T lymphocytes in vitro with the recombinant immunotoxin, LMB-2.” J Immunother. 29(2):208-214, March/April 2006.

Powell Jr., D.J., Parker, L.L. and Rosenberg, S.A. “Large scale depletion of CD25+ regulatory T cells from patient leukapheresis samples.” J Immunother. 28(4):403-411, July/August 2005.

Powell Jr., D.J., Dudley, M.E., Robbins, P.F., and Rosenberg, S.A. “Transition of Late Stage Effector T cells to CD27+ CD28+ Tumor-Reactive Effector Memory T cells in Humans after Adoptive Cell Transfer Therapy.” Blood. 105(1):241-50, 2005.

Robbins, P.F., Dudley, M.E., Wunderlich, J., El-Gamil, M.., Li, Y.F., Zhou, J., Huang, J., Powell Jr., D.J., and Rosenberg, S.A. “Persistence of Transferred Lymphocyte Clonotypes Correlates with Cancer Regression in Patients Receiving Cell Transfer Therapy.” J Immunol. 173(12):7125-30, 2004.

Powell Jr., D.J., and Rosenberg, S.A. “Phenotypic and Functional Maturation of Tumor Antigen-Reactive CD8+ T lymphocytes in Patients Undergoing Multiple Course Peptide Vaccination.” J Immunother. 27(1):36-47, 2004.

Powell Jr., D.J., Eisenlohr, L.C., and Rothstein, J.L. “The RET/PTC3 Oncoprotein: An Immunogenic Thyroid Specific Tumor Antigen.” J Immunol. 170(2): 861-9, 2003.