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).
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, Hancock Wayne W: Ubiquitin-specific Protease-7 Inhibition Impairs Tip60-dependent Foxp3+ T-regulatory Cell Function and Promotes Antitumor Immunity. EBioMedicine 13: 99-112, Nov 2016 Notes: pii: S2352-3964(16)30480-7
Chen Xiao, Yang Yizeng, Berger Ian, Khalid Urooj, Patel Akash, Cai Jenny, Farwell Michael D, Langer Corey, Aggarwal Charu, Albelda Steven M, Katz Sharyn I: Early detection of pemetrexed-induced inhibition of thymidylate synthase in non-small cell lung cancer with FLT-PET imaging. Oncotarget Page: Epub ahead of print, Sep 2016 Notes: doi: 10.18632/oncotarget.12085.
Shaul Merav E, Levy Liran, Sun Jing, Mishalian Inbal, Singhal Sunil, Kapoor Veena, Horng Wenhwai, Fridlender Gil, Albelda Steven M, Fridlender Zvi G: Tumor-associated neutrophils display a distinct N1 profile following TGFβ modulation: A transcriptomics analysis of pro- vs. antitumor TANs. Oncoimmunology 5(11): e1232221, Sep 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, Albelda SM: 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, August 2016 Notes: doi: 10.1158/1078-0432.CCR-15-2133.
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, Jul 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, June 2016 Notes: doi: 10.1158/2326-6066.CIR-15-0263.
Newick K, Moon E, Albelda SM: Chimeric Antigen Receptor T Cell Therapy for Solid Tumors. Molecular Therapy Oncolytics 3: 16006, April 2016 Notes: doi: 10.1038/mto.2016.6.
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, March 2016 Notes: doi: 10.3390/ijms17030322.
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, Feb 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, Jan 2016.
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Last updated: 02/13/2017
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