Wallace, Paul, PhD
Director, Flow and Image Cytometry Facility
Roswell Park Cancer Institute
Dr. Wallace came to RPCI from Dartmouth Medical School where he served as Assistant Professor in the Department of Immunology and Microbiology and a faculty member of the Norris Cotton Cancer Center. Dr. Wallace also was co-director of the Annual Clinical Course on Flow and Image Cytometry.
Dr. Wallace earned his doctoral degree in Immunology and Microbiology at the Medical College of Pennsylvania in 1993 and completed a postdoctoral fellowship in Immunotherapy at Dartmouth Medical School in 1996. He also has held several positions in industry including a tumor immunologist with Zynaxis Cell Science, Inc., Malvern, PA, Senior Scientist at SmithKline and French Research Laboratories, Prussia, PA, and director of the Tumor Immunology Department, SmithKline Clinical Laboratories Immunologies.
Dr. Wallace’s research interests include developing dendritic cell vaccines for colorectal cancer and melanoma. He is co-principal investigator for a Phase I trial investigating biospecfic antibody therapy for non-Hodgkin’s lymphoma, and a Phase I trial using biopecific antibodies to target macrophages in the treatment of glioblastoma multiforme.
Research in his laboratory focuses on the immunotherapy of cancer with differentiated myeloid cells. (i) The use of bispecific antibody armed macrophage activated killer cells (MAK cells) in the treatment of Glioblastoma multiforme and ovarian cancers. (ii) The use of dendritic cells for the therapy of non-Hodgkins lymphoma post autologous stem cell transplant. Mechanisms associated with tumor cell killing mediated by myeloid effector cells and the sequence of events involved in the lytic signals. (i) The role of Fc receptors on monocytes, macrophages and dendritic cells. (ii) Bispecific antibodies and fusion proteins in CD64 targeted immunotherapy of melanoma, prostate cancer and non-Hodkins lymphoma.
Research in Dr. Wallace's laboratory has also looked at the immunotherapy of cancer with differentiated myeloid cells. These studies have focused on the mechanisms associated with tumor cell killing mediated by antibody targeted myeloid effector cells (monocytes, macrophages and granulocytes) and the sequence of events involved in the lytic signals. This work has demonstrated that Fc receptors for IgG (FcgR) are the primary cytotoxic trigger molecules associated with killing by myeloid cells. Based on this information, bispecific antibodies (BsAb) that link FcgR on myeloid effector cells to tumor cells were developed. These BsAb have been used to investigate the killing of tumor cells in vitro, and in clinical trials for treatment of lymphoma and glioma, as well as breast, ovarian and prostate cancer.
Dr. Wallace is a member of the American Association of Immunologists, the American Society of Microbiology, the American Association for the Advancement of Science, the International Society for Analytical Cytology and the Society for Leukocyte Biology. He has authored or co-authored more than 45 journal publications, abstracts or book chapters.
The Flow and Image Cytometry Facility provides standard and advanced flow cytometry capabilities for research and clinical investigations at RPCI. It is a licensed reference laboratory for classification of leukemias and lymphomas by immunophenotyping, for evaluating immunologically-based diseases, for monitoring transplant patients, and for evaluating DNA in solid tumors. It is committed to translational research through the development of new tests. Standard and advanced flow and image cytometry services and capabilities also are provided to basic research scientists.
Key Publications
- Berenson, C. S., Wrona, C. T., Grove, L. J., Maloney, J., Garlipp, M. A., Wallace, P. K., Stewart, C. C., and Sethi, S. Impaired alevolar macrophage responsiveness to Haemophilus antigens in chronic obstructive pulmonary disease, Am. J. Respir. Crit. Care Med. (submitted), 2005.
- Fahey, J. V., Wallace, P. K., Johnson, K., Guyre, P. M., and Wira, C. R. Antigen presentation by human uterine epithelial cells to autologous T cells, Am. J. Reprod. Immunol. (in press), 2005.
- Pauly, J. L., Allison, E. M., Hurley, E. L., Nwogu, C. E., Wallace, P. K., and Paszkiewicz, G. M. Fluorescent human lung macrophages analyzed by spectral confocal laser scanning microscopy and multispectral cytometry, Microsc. Res. Tech. 67: 79-89, 2005.
- Chen, Q., Wang, W.-C., Bruce, R., Li, H., Schleider, D. M., Mulbury, M. J., Bain, M. D., Wallace, P. K., Baumann, H., and Evans, S. S. Central Role of IL-6-Receptor Signal Transducing Chain gp130 in Activation of L-Selectin Adhesion by Fever-Range Thermal Stress, Immunity. 20: 59-70, 2004.
- Ramakrishna, V., Treml, J. F., Vitale, L., Connolly, J. E., O'Neill, T., Smith, P. A., Jones, C. L., He, L.-Z., Goldstein, J. I., Wallace, P. K., Keler, T., and Endres, M. J. Mannose receptor targeting of tumor antigen pmel17 to human dendritic cells directs anti-melanoma T cell responses via multiple HLA molecules, J Immunology. 172: 2845-2852, 2004.
- He, L.-Z., Ramakrishna, V., Connolly, J. E., Wang, X.-T., Smith, P. A., Jones, C. L., Valkova-Valchanova, M., Arunakumari, A., Treml, J. F., Goldstein, J. I., Wallace, P. K., Keler, T., and Endres, M. A novel human cancer vaccine elicits cellular responses to the tumor-associated antigen, human chorionic gonadotropin beta, Clin. Cancer Res. 10: 1920-1927, 2004.
- Bercovici, N., Givan, A. L., Waugh, M. G., Fisher, J. L., Vernel-Pauillac, F., Ernstoff, M. S., Abastado, J. P., and Wallace, P. K. Multiparameter precursor analysis of T-cell responses to antigen, J. Immunol. Methods. 276: 5-17, 2003.
- Guyre, C. A., Fisher, J. L., Waugh, M. G., Wallace, P. K., Tretter, C. G., Ernstoff, M. S., and Barth, R. J. Advantages of hydrophobic culture bags over flasks for the generation of monocyte-derived dendritic cells for clinical applications, J. Immunol. Methods. 262: 85-94, 2002.
- Lewis, L. D., Beelen, A. P., Cole, B. F., Wallace, P. K., Fisher, J. L., Waugh, M. G., Wallace, P. K., Yeaman, G. R., Johnson, K., Collins, J. E., Guyre, P. M., and Wira, C. R. MHC class II expression and antigen presentation by human endometrial cells, J. Steroid Biochem. Mol. Biol. 76: 203-11, 2001.
- Wallace, P. K., Kaufman, P. A., Lewis, L. D., Keler, T., Givan, A. L., Fisher, J. L., Waugh, M. G., Wahner, A. E., Guyre, P. M., Fanger, M. W., and Ernstoff, M. S. Bispecific Antibody-Targeted Phagocytosis of HER-2/neu Expressing Tumor Cells by Myeloid Cells Activated in Vivo, J. Immunol. Methods. 248: 167-182, 2001.
- Wallace, P. K., Tsang, K. Y., Schlom, J., Guyre, P. M., Ernstoff, M. S., and Fanger, M. W. Targeting antigen to FcgRI results in presentation in association with MHC Class I, J. Immunol. Methods. 248: 183-194, 2001.
- Sulahian, T. H., Högger, P., Wahner, A. E., Wardwell, K., Goulding, N. J., Sorg, C., Droste, A., Stehling, M., Wallace, P. K., Morganelli, P. M., and Guyre, P. M. Human monocytes express CD163, which is upregulated by IL-10 and identical to p155, Cytokine. 12: 1312-1321, 2000.
- Wallace, P. K., Romet-Lemonne, J. L., Chokri, M., Fanger, M. W., and Fadul, C. E. Production of macrophage activated killer cells for in vivo targeting to glioblastoma with a bispecific antibody to FcgRI and EGF receptor, Cancer Immunol. Immunother. 49: 493-503, 2000.
- Givan, A. L., Fisher, J. L., Waugh, M. G., Ernstoff, M. S., and Wallace, P. K. A flow cytometric method to estimate the precursor frequencies of cells proliferating in response to specific antigens, J. Immunol. Methods. 230: 99-112, 1999.
- Wallace, P. K., Keler, T., Coleman, K., Fisher, J. L., Vitale, L. A., Graziano, R. F., Guyre, P. M., and Fanger, M. W. Humanized mAb H22 binds the human high affinity Fc receptor for IgG (FcgRI), blocks phagocytosis, and modulates receptor expression, J. Leukoc. Biol. 62: 469-79, 1997.
- Ely, P., Wallace, P. K., Givan, A. L., Graziano, R. F., Guyre, P. M., and Fanger, M. W. Bispecific-armed, interferon gamma-primed macrophage-mediated phagocytosis of malignant non-Hodgkin's lymphoma, Blood. 87: 3813-21, 1996.
- Wallace, P. K., Valone, F. H., and Fanger, M. W. Myeloid cell-targeted cytotoxicity of tumor cells. In: M. W. Fanger (ed.) Bispecific antibodies, pp. 43-76. Austin: R.G. Landes Co., 1995.
- Wallace, P. K., Eisenstein, T. K., Meissler, J. J., Jr., and Morahan, P. S. Decreases in macrophage mediated antitumor activity with aging, Mech. Ageing Dev. 77: 169-84, 1995.
- Wallace, P. K. and Morahan, P. S. Role of macrophages in the immunotherapy of Lewis lung peritoneal carcinomatosis, J. Leukoc. Biol. 56: 41-51, 1994.
- Letwin, B. W., Wallace, P. K., Muirhead, K. A., Hensler, G. L., Kashatus, W. H., and Horan, P. K. An improved clonal excess assay using flow cytometry and B-cell gating, Blood. 75: 1178-85, 1990.


