Description of Research Expertise:
Immuno-gene Therapy for Thoracic Malignancies
Lung cancer and other thoracic malignancies are the leading cause of cancer deaths in the United States today. The Thoracic Oncology Research Laboratory is focusing on the design of new treatment strategies for lung cancer and mesothelioma based on the rapidly evolving disciplines of molecular biology, immunotherapy, and gene therapy.
Dr. Albelda’s research is translational in focus and includes animal models, work with human tumor samples, and the conduct of clinical trials. This work is primarily funded through a recently renewed Program Project from the National Cancer Institute and participation in a number of RO1 grants.
The tumor microenvironment is one area of active study. Studies are underway with the goals of 1) a better understanding of the biology of the tumor microenvironment with a focus on the immunuosuppressive activities of white blood cells and fibroblasts, 2) novel approaches to alter the tumor microenvironment to enhance immunotherapy including studying effects using COX-2 inhibitors, TGFbeta inhibitors, T-regulatory cell inhibitors., antibodies against B-cells, and chemotherapeutic drugs. A second area of interest in the lab is the use of adoptive T cell transfer to treat lung malignancies. Studies are underway to modify T cells in order to make them traffic more efficiently into tumors, to have better killing function, and to resist inactivation by the tumor microenvironment. A T cells targeting cancer-associated fibroblasts is being developed. In addition, Dr. Albelda is closely involved with a number of immunogene clinical trials at Penn using an adenovirus expressing the immune-activator interferon-alpha that is instilled into the pleural space of mesothelioma patients (in collaboration with Dr. Daniel Sterman) and T cells altered to attack the mesothelioma tumor target, mesothelin (in collaboration with Drs. Carl June and Andrew Haas).
Sterman DH, Alley E, Stevenson JP, Friedberg J, Metzger S, Recio A, Moon EK, Haas AR, Vachani A, Katz SI, Sun J, Heitjan D, Hwang WT, Litzky L, Yearley JH, Tan KS, Papasavvas E, Kennedy P, Montaner L, Cengel KA, Simone CB, Culligan M, Langer C, Albelda SM: Pilot and Feasibility Trial of Immuno-Gene Therapy of Malignant Mesothelioma Using Intrapleural Delivery of Adenovirus-Interferon-alpha Combined with Chemotherapy Clinical Cancer Research 22 (15): 3791-3800,2016.
Singhal Sunil, Bhojnagarwala Pratik S, O'Brien Shaun, Moon Edmund K, Garfall Alfred L, Rao Abhishek S, Quatromoni Jon G, Stephen Tom Li, Litzky Leslie, Deshpande Charuhas, Feldman Michael D, Hancock Wayne W, Conejo-Garcia Jose R, Albelda Steven M, Eruslanov Evgeniy B: Origin and Role of a Subset of Tumor-Associated Neutrophils with Antigen-Presenting Cell Features in Early-Stage Human Lung Cancer. Cancer cell 30 (1): 120-35,2016.
Newick Kheng, O'Brien Shaun, Sun Jing, Kapoor Veena, Maceyko Steven, Lo Albert, Pure Ellen, Moon Edmund K, Albelda Steven M: Augmentation of CAR T cell trafficking and antitumor efficacy by blocking protein kinase A (PKA) localization. Cancer immunology research 4 (6): 541-51,2016.
Newick K, Moon E, Albelda SM: Chimeric Antigen Receptor T Cell Therapy for Solid Tumors Molecular Therapy Oncolytics 3 : 16006,2016.
Pietrofesa Ralph A, Velalopoulou Anastasia, Albelda Steven M, Christofidou-Solomidou Melpo: Asbestos Induces Oxidative Stress and Activation of Nrf2 Signaling in Murine Macrophages: Chemopreventive Role of the Synthetic Lignan Secoisolariciresinol Diglucoside (LGM2605). International journal of molecular sciences 17 (3): 322,2016.
Pietrofesa Ralph A, Velalopoulou Anastasia, Arguiri Evguenia, Menges Craig W, Testa Joseph R, Hwang Wei-Ting, Albelda Steven M, Christofidou-Solomidou Melpo: Flaxseed lignans enriched in secoisolariciresinol diglucoside prevent acute asbestos-induced peritoneal inflammation in mice. Carcinogenesis 37 (2): 177-87,2016.
Moon Edmund K, Ranganathan Raghuveer, Eruslanov Evgeniy, Kim Soyeon, Newick Kheng, O'Brien Shaun, Lo Albert, Liu Xiaojun, Zhao Yangbing, Albelda Steven M: Blockade of Programmed Death 1 Augments the Ability of Human T Cells Engineered to Target NY-ESO-1 to Control Tumor Growth after Adoptive Transfer. Clinical Cancer Research : an official journal of the American Association for Cancer Research 22 (2): 436-47,2016.
Kennedy Gregory T, Okusanya Olugbenga T, Keating Jane J, Heitjan Daniel F, Deshpande Charuhas, Litzky Leslie A, Albelda Steven M, Drebin Jeffrey A, Nie Shuming, Low Philip S, Singhal Sunil: The Optical Biopsy: A Novel Technique for Rapid Intraoperative Diagnosis of Primary Pulmonary Adenocarcinomas. Annals of surgery 262 (4): 602-9,2015.
Liu Yuhong, O'Leary Claire E, Wang Liang-Chuan S, Bhatti Tricia R, Dai Ning, Kapoor Veena, Liu Peihui, Mei Junjie, Guo Lei, Oliver Paula M, Albelda Steven M, Worthen G Scott: CD11b+Ly6G+ cells inhibit tumor growth by suppressing IL-17 production at early stages of tumorigenesis. Oncoimmunology 5 (1): e1061175,2015.
Wang, E., Wang, L.C., Tsai, C.Y., Bhoj, V., Gershenson, Z., Moon, E., Newick, K., Sun, J., Lo A., Baradet, T., Feldman, M.D., Barrett, D., Puré, E., Albelda, S.M., Milone, M.C.: Generation of Potent T-cell Immunotherapy for Cancer Using DAP12-Based, Multichain, Chimeric Immunoreceptors Cancer Immunology Research 3 (7): 815-26,2015.
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