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).
Davis Richard W, Papasavvas Emmanouil, Klampatsa Astero, Putt Mary, Montaner Luis J, Culligan Melissa J, McNulty Sally, Friedberg Joseph S, Simone Charles B, Singhal Sunil, Albelda Steven M, Cengel Keith A, Busch Theresa M: A preclinical model to investigate the role of surgically-induced inflammation in tumor responses to intraoperative photodynamic therapy. Lasers in surgery and medicine 50 (5): 440-450,2018.
Bengsch Bertram, Ohtani Takuya, Khan Omar, Setty Manu, Manne Sasikanth, O'Brien Shaun, Gherardini Pier Federico, Herati Ramin Sedaghat, Huang Alexander C, Chang Kyong-Mi, Newell Evan W, Bovenschen Niels, Pe'er Dana, Albelda Steven M, Wherry E John: Epigenomic-Guided Mass Cytometry Profiling Reveals Disease-Specific Features of Exhausted CD8 T Cells. Immunity 48 (5): 1029-1045.e5,2018.
Aggarwal Charu, Haas Andrew R, Metzger Susan, Aguilar Laura K, Aguilar-Cordova Estuardo, Manzanera Andrea G, Gómez-Hernández Gregoria, Katz Sharyn I, Alley Evan W, Evans Tracey L, Bauml Joshua M, Cohen Roger B, Langer Corey J, Albelda Steven M, Sterman Daniel H: Phase I Study of Intrapleural Gene-Mediated Cytotoxic Immunotherapy in Patients with Malignant Pleural Effusion. Molecular therapy : the journal of the American Society of Gene Therapy 26 (5): 1198-1205,2018.
Scherpereel Arnaud, Wallyn Frederic, Albelda Steven M, Munck Camille: Novel therapies for malignant pleural mesothelioma. The Lancet. Oncology 19 (3): e161-e172,2018.
Pietrofesa Ralph A, Chatterjee Shampa, Park Kyewon, Arguiri Evguenia, Albelda Steven M, Christofidou-Solomidou Melpo: Synthetic Lignan Secoisolariciresinol Diglucoside (LGM2605) Reduces Asbestos-Induced Cytotoxicity in an Nrf2-Dependent and -Independent Manner. Antioxidants (Basel, Switzerland) 7 (3): pii E38,2018.
Negorev Dmitri, Beier Ulf H, Zhang Tianyi, Quatromoni Jon G, Bhojnagarwala Pratik, Albelda Steven M, Singhal Sunil, Eruslanov Evgeniy, Lohoff Falk W, Levine Matthew H, Diamond Joshua M, Christie Jason D, Hancock Wayne W, Akimova Tatiana: Human neutrophils can mimic myeloid-derived suppressor cells (PMN-MDSC) and suppress microbead or lectin-induced T cell proliferation through artefactual mechanisms. Scientific reports 8 (1): 3135,2018.
Moon Edmund K, Wang Liang-Chuan S, Bekdache Kheng, Lynn Rachel C, Lo Albert, Thorne Stephen H, Albelda Steven M: Intra-tumoral delivery of CXCL11 via a vaccinia virus, but not by modified T cells, enhances the efficacy of adoptive T cell therapy and vaccines. Oncoimmunology 7 (3): e1395997,2018.
Aggarwal Charu, Wang Xingmei, Ranganathan Anjana, Torigian Drew, Troxel Andrea, Evans Tracey, Cohen Roger B, Vaidya Bhavesh, Rao Chandra, Connelly Mark, Vachani Anil, Langer Corey, Albelda Steven: Circulating tumor cells as a predictive biomarker in patients with small cell lung cancer undergoing chemotherapy. Lung cancer (Amsterdam, Netherlands) 112 : 118-125,2017.
Pietrofesa RA, Woodruff P, Hwang WT, Patel P, Chatterjee S, Albelda SM, Christofidou-Solomidou M: The synthetic lignan secoisolariciresinol diglucoside prevents asbestos-induced NLRP3 inflammasome activation in murine macrophages. Oxidative medicine and cellular longevity 2017 : 7395238,2017.
Akimova T, Zhang T, Negorev D, Singhal S, Stadanlick J, Rao A, Annunziata M, Levine MH, Beier UH, Diamond JM, Christie JD, Albelda SM, Eruslanov EB, Hancock WW: Human lung tumor FOXP3+ Tregs upregulate four "Treg-locking" transcription factors. JCI Insight 2 (16): pii 94075,2017.
View all publications