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Chemokine-based therapy for lung cancer

Institution: University of California, Los Angeles
Investigator(s): Sherven Sharma, Ph.D.
Award Cycle: 2001 (Cycle 10) Grant #: 10RT-0053 Award: $416,940
Subject Area: Cancer
Award Type: Research Project Awards
Abstracts

Initial Award Abstract
The overwhelming majority of lung cancers (greater than 90 %) are caused by cigarette smoking. Lung cancer is the leading cause of cancer death in the United States and more than 140,000 Americans died from lung cancer in 1999. Since January 1st 2000, more than 10,000 smokers in America have died from lung cancer. There are currently fifty million smokers in the U.S. and another fifty million ex-smokers. This means that approximately one third of the population of U.S. is at high risk for this terrible disease. With the existing therapy, patients with lung cancer have a poor prognosis. Less than 15 % of lung cancer patients survive more than 5 years. Failure of conventional therapies has led to an intensive search for new forms of treatment. Our research focuses on boosting the body’s immune system against lung cancer by utilizing secondary lymphoid chemokine (SLC) levels in the body. Chemokines, a group of homologous yet functionally divergent proteins, directly mediate leukocyte (a type of white blood cell) migration and activation and play a role in regulating angiogenesis (formation of new blood vessels). Chemokines also function in maintaining our immune systems as well. SLC attracts certain immune cells - specifically dendritic cells and T lymphocytes - from the body that help fight cancer. This type of immunotheraputic treatment is able to completely cure cancer in mice. In order to develop SLC immunotherapy for lung cancer patients, this research focuses on specifically determining how this therapy works in animal models. The findings of this study can be taken from 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

SLC reduces pulmonary tumor burden in spontaneous murine bronchoalveolar cell carcinoma.
Periodical: Cancer Research Index Medicus:
Authors: Sharma S, Stolina M, Zhu L, Lin Y, Batra RK, Huang M, Strieter R, and Dubinett SM ART
Yr: 2991 Vol: 61 Nbr: 17 Abs: Pg: 6406-12

Non-small cell lung cancer cyclooxygenase-2-dependent invasion is mediated by CD44.
Periodical: Journal of Biological Chemistry Index Medicus:
Authors: Dohadwala M, Luo J, Lin Y Dougherty GJ, Sharma S, Huang M, Pold M, Batra RK, Dubinett SM ART
Yr: 2001 Vol: 276 Nbr: 24 Abs: Pg: 20809-12

Ectopic expression of the thyroperoxidase gene augments radiolodide uptake and retention mediated by the socium iodide symporter in non-small cell lung cancer.
Periodical: Proceedings of the National Academy of Sciences of the United States of America Index Medicus:
Authors: Hunag M, Batra RK, Kogai T, Lin YQ, Hershman JM, Lichtenstein A, Sharma S, et al ART
Yr: 2000 Vol: 97 Nbr: 15 Abs: Pg: 8519-24

SLC/CCL21-mediated anti-tumor responses require IFNy, MIG/CXCL9 and IP-10/CXCL10.
Periodical: Molecular Cancer Research Index Medicus:
Authors: Sharma S, Yang SC, Hillinger S, Zhu L, Huang M, Batra RK, Lin JF, Burdick MD, et al ART
Yr: 2003 Vol: 2 Nbr: 1 Abs: Pg: 22

Tumor COX-2 dependent regulation of murine dendritic cell function.
Periodical: Clinical Cancer Research Index Medicus:
Authors: Sharma S, Stolina M, Baratelli F, Lin JF, Atianzar K, Zhu L, Lin Y, et al ART
Yr: 2003 Vol: 9 Nbr: Abs: Pg: 961-968

Non-small cell lung cancer-derived soluble mediators enhance apoptosis in T lymphocytes through an I kappa B kinase-dependent mechanism.
Periodical: Cancer Research Index Medicus:
Authors: Batra R, Lin Y, Gardner B, Luo J, Dohadwala M, Sharma S, Dubinett SM ART
Yr: 2003 Vol: 63 Nbr: Abs: Pg: 642-646

Abnormal IL-10Ralpha expression contributes to the maintenance of elevated COX-2 in non-small cell lung cancer cells.
Periodical: Cancer Research Index Medicus:
Authors: Heuze-Vourc'h N, Krysan K, Batra RK, Sharma S, Dubinett SM ART
Yr: 2003 Vol: 63 Nbr: Abs: Pg: 766-770

IL-10 mediates the sigma receptor-dependent suppression of antitumor immunity.
Periodical: Journal of Immunology Index Medicus:
Authors: Zhu LX, Sharma S, Gardner B, Escuadro B, Atianzar K, Tashkin D, Dubinett SM ART
Yr: 2003 Vol: 170 Nbr: Abs: Pg: 3585-3591

Secondary lymphoid tissue chemokine mediates T cell-dependent antitumor responses in vivo.
Periodical: Journal of Immunology Index Medicus:
Authors: Sharma S, Stolina M, Luo J, Strieter RM, Burdick M, Zhu LI, Batra RK, Dubinett SM ART
Yr: 2000 Vol: 164 Nbr: Abs: Pg: 4558 - 4563

Secondary lymphoid organ chemokine reduces pulmonary tumor burden in spontaneous murine bronchoalveolar cell carcinoma.
Periodical: Cancer Research Index Medicus:
Authors: Sharma S, Stolina M, Zhu L, Lin Y, Batra R, Huang M Strieter R, Dubinett SM ART
Yr: 2001 Vol: 1;61 Nbr: 17 Abs: Pg: 6406 - 6412

Over expression of CCL-21/Secondary lymphoid tissue chemokine in human dendritic cells augments patacrine chemotactic activities for lymphocytes and antigen presenting cells.
Periodical: Molecular Cancer Research Index Medicus:
Authors: Sharma S, Riedl K, Baratelli F, Batra RK, Yang SC, Luo J, Escuadro B, Figlin R, et al. ART
Yr: 2003 Vol: 2 Nbr: Abs: Pg: 35

Cyclooxygenase 2-dependent regulation of antitumor immunity in lung cancer.
Periodical: Methods in Molecular Medicine Index Medicus:
Authors: Sharma S, Huang M, Dohadwala M, Pold M, Batra RK, Dubinett SM, et al. ART
Yr: 2003 Vol: 75 Nbr: Abs: Pg: 723 - 736

Intratumoral therapy with cytokine gene-modified dentritic cells in murine lung cancer models.
Periodical: Methods in Molecular Medicine Index Medicus:
Authors: Sharma S, Yang SC, Batra RK, Dubinett SM ART
Yr: 2003 Vol: 75 Nbr: Abs: Pg: 711 - 722

EBV-induced molecule 1 ligand chemokine (ELC/CCL19) promotes IFN-gamma-dependent antitumor responses in a lung cancer model.
Periodical: Journal of Immunology Index Medicus:
Authors: Sharma S, Hillinger S, Yang SC, Zhu L, Huang M Duckett R, Atianzar K, Batra RK, et al. ART
Yr: 2003 Vol: 171 Nbr: 12 Abs: Pg: 6457 - 6465

Interleukin-7 gene-modified dendritic cells reduce pulmonary tumor burden in spontaneous murine bronchoalveolar cell carcinoma.
Periodical: Human Gene Therapy Index Medicus:
Authors: Sharma S, Batra RK, Yang SC, Hillinger S, Zhu L, Atianzar K, Strieter RM, et al ART
Yr: 2003 Vol: 14 Nbr: 16 Abs: Pg: 1511 - 1524

Tumor cyclooxygenase 2-dependent suppression of dendritic cell function.
Periodical: Clinical Cancer Research Index Medicus:
Authors: Sharma S, Stolina M, Yang SC, Baratelli F, Lin JF, Atianzar K, Luo J, Zhu L, Lin Y, et al. ART
Yr: 2003 Vol: 9 Nbr: 3 Abs: Pg: 961 - 968

Intratumoral administration of dendritic cells overexpressing CCL21 generates systemic antitumor responses and confers tumor immunity.
Periodical: Clinical Cancer Research Index Medicus:
Authors: Sharma S, Yang SC, Hillinger S, Riedl K, Zhang L, Zhu L, Huang M, Atianzar K, et al. ART
Yr: 2004 Vol: 10 Nbr: 8 Abs: Pg: 2891 - 2901

Tumor COX-2/PGE2 dependent promotion of FOXP3 expression and CD4+CD25+ T regulatory cell activities in lung cancer.
Periodical: Cancer Research Index Medicus:
Authors: Sharma S, Yang SC, Zhu L, Reckamp K, Gardner B, Baratelli F, Zhang L, Huang M, et al. ART
Yr: 2005 Vol: 65 Nbr: 14 Abs: Pg: 6275 - 6281

COX-2 inhibition promotes IFNy-dependent enhancement of anti-tumor immunity.
Periodical: Journal of Immunology Index Medicus:
Authors: Sharma S, Zhu L, Hillinger S, Yang SC, Gardner B, Kuo B, Reckamp K. Strieter RM, et al. ART
Yr: 2005 Vol: 175 Nbr: 2 Abs: Pg: 813 - 819

PGE2 induces FOXP3 gene expression and T regulatory function in human CD4+ T cells.
Periodical: Journal of Immunology Index Medicus:
Authors: Sharma S, Baratelli F, Lin Y, Zhu L, Yang SC, Heuze-Voure'h N, Zeng G, et al. ART
Yr: 2005 Vol: 175 Nbr: 3 Abs: Pg: 1483 - 1490

CXC chemokines: angiogenesis, immunoangiostasis, and metastases in lung cancer.
Periodical: Annals of the New York Academy of Sciences Index Medicus:
Authors: Sharma S, Strieter RM, Belperio JA, Burdick MD, Dubinett SM Keane MP ART
Yr: 2004 Vol: 1028 Nbr: Abs: Pg: 351 - 360