title: C-C chemokine receptor type-4 transduction of T cells enhances interaction with dendritic cells, tumor infiltration and therapeutic efficacy of adoptive T cell transfer.
abstract: T cell infiltration at the tumor site has been identified as a major predictor for the efficacy of adoptive T cell therapy. The chemokine C-C motif ligand 22 (CCL22) is highly expressed by immune cells in murine and human pancreatic cancer. Expression of its corresponding receptor, C-C chemokine receptor type 4 (CCR4), is restricted to regulatory T cells (Treg). We show that transduction of cytotoxic T cells (CTL) with CCR4 enhances their immigration into a pancreatic cancer model. Further, we show that binding of CCR4 with CCL22 strengthens the binding of T cell LFA-1 to dendritic cell (DC) ICAM-1 and increases CTL activation.In vivo, in a model of subcutaneous pancreatic cancer, treatment of tumor-bearing mice with CCR4-transduced CTL led to the eradication of established tumors in 40% of the mice. In conclusion, CCR4 overexpression in CTL is a promising therapeutic strategy to enhance the efficacy of adoptive T cell transfer (ACT).
authors.affiliation: Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Internal Medicine IV, Klinikum der Ludwig-Maximilians-Universität München, Member of the German Center for Lung Research , Munich, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Rapp
authors.affiliation: Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Internal Medicine IV, Klinikum der Ludwig-Maximilians-Universität München, Member of the German Center for Lung Research , Munich, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Grassmann
authors.affiliation: Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Internal Medicine IV, Klinikum der Ludwig-Maximilians-Universität München, Member of the German Center for Lung Research , Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Chaloupka
authors.affiliation: Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Internal Medicine IV, Klinikum der Ludwig-Maximilians-Universität München, Member of the German Center for Lung Research , Munich, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Layritz
authors.affiliation: Department of Internal Medicine III and Comprehensive Cancer Center, Klinikum der Ludwig-Maximilians-Universität München , Munich, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Kruger
authors.affiliation: Institute of Pathology, Ludwig-Maximilians-Universität München , Munich, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Ormanns
authors.affiliation: Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Internal Medicine IV, Klinikum der Ludwig-Maximilians-Universität München, Member of the German Center for Lung Research , Munich, Germany.
authors.forename: Felicitas
authors.initials: F
authors.lastname: Rataj
authors.affiliation: Department of Surgery, Klinikum Rechts der Isar, Technische Universität München , Munich, Germany.
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Janssen
authors.affiliation: Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Internal Medicine IV, Klinikum der Ludwig-Maximilians-Universität München, Member of the German Center for Lung Research , Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Endres
authors.affiliation: Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Internal Medicine IV, Klinikum der Ludwig-Maximilians-Universität München, Member of the German Center for Lung Research, Munich, Germany; Department of Internal Medicine IV, Division of Gastroenterology, Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Anz
authors.affiliation: Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Internal Medicine IV, Klinikum der Ludwig-Maximilians-Universität München, Member of the German Center for Lung Research , Munich, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kobold
keywords: Adoptive transfer; CCL22; CCR4; LFA-1; chemokine; tumor