title: CCL21 Chemokine Therapy for Lung Cancer.
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.
authors.affiliation: 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.
authors.forename: Sherven
authors.initials: S
authors.lastname: Sharma
authors.affiliation: 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.
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.affiliation: 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.
authors.forename: Minu K
authors.initials: MK
authors.lastname: Srivastava
authors.affiliation: Molecular Gene Medicine Laboratory, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
authors.forename: Marni
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authors.lastname: Harris-White
authors.affiliation: 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.
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: Jay M
authors.initials: JM
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Fran
authors.initials: F
authors.lastname: Rosen
authors.affiliation: 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.
authors.forename: Gina
authors.initials: G
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Gerald
authors.initials: G
authors.lastname: Wang
authors.affiliation: Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA.
authors.forename: Valerie
authors.initials: V
authors.lastname: Kickhoefer
authors.affiliation: Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA.
authors.forename: Leonard H
authors.initials: LH
authors.lastname: Rome
authors.affiliation: Department of Medicine, UCLA Lung Cancer Research Program, David Geffen School of Medicine at UCLA.
authors.forename: Felicita
authors.initials: F
authors.lastname: Baratelli
authors.affiliation: Department of Medicine, UCLA Lung Cancer Research Program, David Geffen School of Medicine at UCLA.
authors.forename: Maie
authors.initials: M
authors.lastname: St John
authors.affiliation: Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, California.
authors.forename: Karen
authors.initials: K
authors.lastname: Reckamp
authors.affiliation: 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.
authors.forename: Seok
authors.initials: S
authors.lastname: Chul-Yang
authors.affiliation: Division of Thoracic Surgery, University Hospital Zurich, Switzerland.
authors.forename: Sven
authors.initials: S
authors.lastname: Hillinger
authors.affiliation: Department of Medicine, University of Virginia, Charlottesville, VA, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Strieter
authors.affiliation: 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.
authors.forename: Steven
authors.initials: S
authors.lastname: Dubinett