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Immune Targeted Therapy for Lung Cancer

Institution: University of California, Los Angeles
Investigator(s): Sherven Sharma, Ph.D.
Award Cycle: 2006 (Cycle 15) Grant #: 15RT-0207 Award: $419,500
Subject Area: Cancer
Award Type: Research Project Awards
Abstracts

Initial Award Abstract
Lung cancer is the leading cause of cancer death in the United States. Last year lung cancer caused more than 162,000 deaths in the US. Epidemiological studies show a strong correlation between tobacco smoking and lung cancer. There are currently fifty million smokers in the US and another fifty million former smokers. Thus, approximately one third of the US population is at high risk for this disease. With the existing therapeutic efforts, patients with lung cancer have a poor prognosis and only 15 % survive 5 years following diagnosis. Failure of conventional therapies has led to an intensive search for new forms of treatment. Our efforts to produce effective cancer therapy focuses on methods to restore immune deficits in lung cancer patients by utilizing specialized cells from the body known as dendritic cells that we genetically modify in our laboratory to secrete proteins called secondary lymphoid chemokine and interleukin-7. These therapeutic proteins when secreted from dendritic cells help mice reject lung cancer. Lung cancer patients have dramatically decreased numbers of circulating competent dendritic cells. To increase the numbers of dendritic cells in the cancer bearing host we will administer two proteins GMCSF and interleukin 4. We are performing experiments in our laboratory that will aid us in understanding this form of therapy in mice with lung cancer. The findings of this study can be taken from the research laboratory to lung cancer clinical trials. Thus, results of this study may have a major impact on the treatment of patients with lung cancer.
Publications

Intrapulomonary administration of CCL21 gene-modified dendritic cells reduces tumor burden in spontaneous murine bronchoalveolar cell carcinoma
Periodical: Cancer Research Index Medicus:
Authors: Yang, S.C., Batra, R.K., Hillinger, S., Rekamp, K.L., Strieter, R.M., Dubinett, S., Sharma ART
Yr: 2006 Vol: 66 Nbr: 6 Abs: Pg: 3205-13

CCl19 reduces tumour burden in a model of advanced lung cancer
Periodical: British Journal of Cancer Index Medicus:
Authors: Hillinger, S., Yang, S.C., Btra, R.K., Strieter, R.M., Weder, W., Dubinett, S.M, Sharma, S ART
Yr: 2006 Vol: 94 Nbr: 7 Abs: Pg: 1029-34

Inflammation in lung carcinogenesis: new targets for lung cancer chemoprevention and treatment
Periodical: Critical Reviews in Oncology/Hematolgy Index Medicus:
Authors: Lee, J.M., Yanagawa, J., Peebles, K.A., Sharma, S., Mao, J.T., Dubinett, S.M. ART
Yr: 2008 Vol: 66 Nbr: 3 Abs: Pg: 208-17

Tumor response to combination celecoxib and erlotinib therapy in no-smal cell lung cancer is assocated with a low baseline matrix mettalloproteinase-9 and a decline in serum-soluable E-caderherin
Periodical: Journal of Thoracic Oncology Index Medicus:
Authors: Reckamp, K.L, Gardner, B.K., Figlin, R.A., Elashoff, D., Kryasan, K., Dohadwala, M., Mao, ART
Yr: 2008 Vol: 2 Nbr: Abs: Pg: 117-24

Immunolgic Approaches to Lung Cancer Therapy
Periodical: Lung Cancer Index Medicus:
Authors: Lee, J.M., Dubinett, S.M., Sharma, S. ART
Yr: 2007 Vol: 3 Edition Nbr: Abs: Pg:

Inflammation and lung carcinogenesis: applying new findings in prevention and treatment
Periodical: Expert Review of Anticancer Therapy Index Medicus:
Authors: Peebles, K.A., Lee, J.M., Mao, J.T., Harza, S., Reckamp, K.L., Krysa, K., Dohadwala, M., ART
Yr: 2007 Vol: 7 Nbr: 10 Abs: Pg: 1405-21

IL-7 promotes CXCR3 ligand-dependent T cell antitumor reactivity in lung cancer.
Periodical: Journal of Immunology Index Medicus:
Authors: Anderson A,Yang S, Huang M, Zhu L, Kar U, Batra R, Elashoff D;StrieterR;Dubinett S SharmaS ART
Yr: 2009 Vol: 182 Nbr: 11 Abs: Pg: 6951-6958