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).
Pietrofesa RA, Woodruff P, Hwang WT, Patel P, Chatterjee S, Albelda SM: 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: Human lung tumor FOXP3+ Tregs upregulate four "Treg-locking" transcription factors. JCI Insight 2 (16): 2017.
Moon EK, Langer CJ: The era of checkpoint blockade in lung cancer: taking the brakes off the immune system. Annals of the American Thoracic Society 14 (8): 1248-1260,2017.
Chen X, Yang Y, Berger I, Khalid U, Patel A, Cai J, Farwell MD, Langer C, Aggarwal C, Albelda SM: Early detection of pemetrexed-induced inhibition of thymidylate synthase in non-small cell lung cancer with FLT-PET imaging. Oncotarget 8 (15): 24213-24223,2017.
Wang Liqing, Kumar Suresh, Dahiya Satinder, Wang Feng, Wu Jian, Newick Kheng, Han Rongxiang, Samanta Arabinda, Beier Ulf H, Akimova Tatiana, Bhatti Tricia R, Nicholson Benjamin, Kodrasov Mathew P, Agarwal Saket, Sterner David E, Gu Wei, Weinstock Joseph, Butt Tauseef R, Albelda Steven M: Ubiquitin-specific Protease-7 Inhibition Impairs Tip60-dependent Foxp3+ T-regulatory Cell Function and Promotes Antitumor Immunity. EBioMedicine 13 : 99-112,2016.
Shaul ME, Levy L, Sun J, Mishalian I, Singhal S, Kapoor V, Horng W, Fridlender G, Albelda SM: Tumor-associated neutrophils display a distinct N1 profile following TGFβ modulation: A transcriptomics analysis of pro- vs. antitumor TANs. Oncoimmunology 5 (11): e1232221,2016.
Sterman DH, Alley E, Stevenson JP, Friedberg J, Metzger S, Recio A, Moon EK, Haas AR, Vachani A, Katz SI, Sun J, Heitjan DF, Hwang WT, Litzky L, Yearley JH, Tan KS, Papasavvas E, Kennedy P, Montaner LJ, Cengel KA, Simone CB, Culligan M, Langer CJ: Pilot and Feasibility Trial Evaluating Immuno-Gene Therapy of Malignant Mesothelioma Using Intrapleural Delivery of Adenovirus-Interferon-alpha Combined with Chemotherapy Clinical Cancer Research 22 (15): 3791-3800,2016.
Condamine T, Dominguez GA, Youn JI, Kossenkov AV, Mony S, Alicea-Torres K, Tcyganov E, Hashimoto A, Nefedova Y, Lin C, Partlova S, Garfall A, Vogl DT, Xu X, Knight SC, Malietzis G, Lee GH, Eruslanov E, Albelda SM, Wang X, Mehta JL, Bewtra M, Rustgi A, Hockstein N, Witt R, Masters G, Nam B, Smirnov D, Sepulveda MA: Lectin-type oxidized LDL receptor-1 distinguishes population of human polymorphonuclear myeloid-derived suppressor cells in cancer patients. Science Immunology 1 (2): 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: 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: Augmentation of CAR T cell trafficking and antitumor efficacy by blocking protein kinase A (PKA) localization. Cancer immunology research 4 (6): 541-51,2016.
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