• Primary Faculty Profiles
• Bankert, Richard, Ph.D., V.M.D., Professor
• Bianco, Piero, Ph.D., Associate Professor
• Campagnari, Anthony, Ph.D., Professor
• Collins, Arlene, Ph.D., Associate Professor
• Connell, Terry, Ph.D., Professor
• Egilmez, Nejat, Ph.D., Associate Professor
• Hakansson, Anders, Ph.D., Assistant Professor
• Hay, John, Ph.D., Professor
• Jacobs, Amy, Ph.D., Assistant Professor
• Melendy, Thomas, Ph.D., Associate Professor
• Panepinto, John, Ph.D., Assistant Professor
• Read, Laurie, Ph.D., Professor
• Russell, Michael, Ph.D., Professor
• Ruyechan, William, Ph.D., Professor and Chairman
• Thacore, Harshad, Ph.D., Associate Professor
• Williams, Noreen, Ph.D., Professor
• Adjunct Faculty Profiles
• Departmental Publications
• Career Opportunities
• The Witebsky Center
• Seminars

Faculty and Research

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Education:

1973, Ph.D. U. Penn Grad. Sch. Arts & Sciences, Phila., PA
1970-19731, NIH Postdoc, U. Penn, Sch. of Med., Philadelphia, PA
1968, U. Penn Sch. of Vet. Med., Phiadelphia, PA
1962, Bachelor of Arts, Gettysburg College, Gettysburg, PA

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Research Interests:

We are studying the immune response of cancer patients to their tumors. The inability of cancer patients to eradicate their tumors and the ineffectiveness of cancer vaccines are not due simply to a failure to generate tumor-specific lymphocytes or to the lack of these lymphocytes reaching the tumor.  Our data support the notion that once present in the tumor microenvironment tumor specific lymphocytes become hypo-responsive and fail to attack and kill tumor cells. This hypo-responsiveness is due to an arrest or checkpoint in the T cell receptor signaling machinery. Our studies are designed to gain a better understanding of the molecular events that are responsible for the signaling arrest and to determine ways that this arrest can be reversed.

Our goal is to design new immunotherapeutic strategies for patients with advanced cancer.  Our approach is to reactivate tumor specific lymphocytes that exist within the tumor microenvironment using a variety of different ways we have found to reverse the signaling arrest in these cells.  By reactivating the tumor specific cells in one tumor mass it is expected that there will be a release of tumor antigens (from the dead and dying cells) into the blood thereby inducing a systemic anti-tumor immunity that will seek out and eliminate tumor cells at distant untreated sites. These therapeutic strategies, called in situ vaccinations, are being developed in our lab using local and sustained delivery of biologically active factors, called cytokines into tumors using cytokine loaded liposomes, biodegradable microspheres and oncolytic viruses that have been genetically engineered to produce and release cytokines.  Our strategies are being tested pre-clinically in a model developed in our lab in which non-disrupted human tumor tissues are engrafted into immunodeficient mice.  The human tumor xenografts include both the tumor, the tumor associated stromal fibroblalsts and the inflammatory cells including lymphocytes.  This model has made it possible for us to evaluate and predict the therapeutic efficacy of our protocols before we try them in patients. We are also working in close collaboration with cancer clinicians and surgeons to translate our findings into the clinic with the treatment of cancer patients.

Currently there is insufficient knowledge of how the human immune system is activated and regulated within tumor microenvironments.  It will be essential to define the molecular and cellular events that shape and alter the function of human tumor associated lymphocytes in order to design and develop the most therapeutically effective immunotherapies for cancer. To this end we are investigating how different cells within the tumor microenvironment (including fibroblasts, inflammatory leukocytes, and tumor cells) and their secreted products amplify or arrest lymphocyte responses to tumor cells.

Relevant references:

Broderick, L., Yokota, S.J., Reineke, J., Mathiowitz, E., Stewart, C.C., Barcos, M., Kelleher, R.J., Jr. and Bankert, R.B.  Human CD4+ effector memory T cells persisting in the microenvironment of lung cancer xenografts are activated by local delivery of IL-12 to proliferate, produce IFN-g, and eradicate tumor cells.  J. Immunol. 174: 898-906, 2005.  PMID: 15634912

Broderick, L., Brooks, S.P., Takita, H., Baer, A.N., Bernstein, J.M. and Bankert, R.B.  IL-12 reverses anergy to T cell receptor triggering in human lung tumor-associated memory T cells.  Clin. Immunol. 118: 159-169, 2006.  PMID: 16271513

Broderick, L. and Bankert, R.B.  Memory T Cells in Human Tumor and Chronic Inflammatory Microenvironments:  Sleeping Beauties Re-awakened by Cytokine Kiss (Review).  Immunol. Invest. 35: 1-18, 2006.  PMID: 16916760

Broderick, L. and Bankert, R.B.  Membrane-associated TGF-β1 inhibits human memory T cell signaling in malignant and nonmalignant inflammatory microenvironments.  J. Immunol. 177: 3082-3088, 2006.  PMID: 16920945

Nazareth, M.R., Broderick, L., Simpson-Abelson, M.R., Kelleher, R.J., Jr., Yokota, S.J. and Bankert, R.B. Characterization of Human Lung Tumor-Associated Fibroblasts and Their Ability to Modulate the Activation of Tumor-Associated T Cells.  J. Immunol. 178: 5552-5562, 2007.  PMID: 17442937

Simpson-Abelson, M. and Bankert, R.B.  Targeting the TCR signaling checkpoint: a therapeutic strategy to reactivate memory T cells in the tumor microenvironment.  Expert Opin Ther Targets 12: 477-490, 2008  PMID: 18348683

Simpson-Abelson, M.R., Sonnenberg, G.F., Takita, H., Yokota, S.J., Conway, T.J., Jr., Kelleher, R.J., Jr., Shultz, L.D., Barcos, M. and Bankert, R.B.  Long-term engraftment and expansion of tumor-derived memory T cells following the implantation of non-disrupted pieces of human lung tumor into NOD-scid IL2Rγnull mice.  J. Immunol. 180: 7009-7018, 2008.  PMID: 18453623