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Int Trends Immun. 2013 Jan;1(1):10-15.

CCL21 Chemokine Therapy for Lung Cancer.

Author information

1
Department of Medicine, UCLA Lung Cancer Research Program, David Geffen School of Medicine at UCLA ; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA ; Molecular Gene Medicine Laboratory, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
2
Department of Medicine, UCLA Lung Cancer Research Program, David Geffen School of Medicine at UCLA ; Molecular Gene Medicine Laboratory, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
3
Molecular Gene Medicine Laboratory, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
4
Department of Medicine, UCLA Lung Cancer Research Program, David Geffen School of Medicine at UCLA ; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA.
5
Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA.
6
Department of Medicine, UCLA Lung Cancer Research Program, David Geffen School of Medicine at UCLA.
7
Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, California.
8
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
9
Division of Thoracic Surgery, University Hospital Zurich, Switzerland.
10
Department of Medicine, University of Virginia, Charlottesville, VA, USA.

Abstract

Lung cancer remains a challenging health problem with more than 1.1 million deaths worldwide annually. With current therapy, the long term survival for the majority of lung cancer patients remains low, thus new therapeutic strategies are needed. One such strategy would be to develop immune therapy for lung cancer. Immune approaches remain attractive because although surgery, chemotherapy, and radiotherapy alone or in combination produce response rates in all histological types of lung cancer, relapse is frequent. Strategies that harness the immune system to react against tumors can be integrated with existing forms of therapy for optimal responses toward this devastating disease. Both antigen presenting cell (APC) and T cell activities are reduced in the lung tumor microenvironment. In this review we discuss our experience with efforts to restore host APC and T cell activities in the lung cancer microenvironment by intratumoral administration of dendritic cells (DC) expressing the CCR7 receptor ligand CCL21 (secondary lymphoid chemokine, SLC). Based on the results demonstrating that CCL21 is an effective anti cancer agent in the pre-clinical lung tumor model systems, a phase I clinical trial was initiated using intratumoral injection of CCL21 gene modified autologous DC in lung cancer. Results from the trial thus far indicate tolerability, immune enhancement and tumor shrinkage via this approach.

PMID:
25264541
PMCID:
PMC4175527

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