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. (3rd March 2016)

• Record Type: Journal Article
• Authors: Rapp, Moritz; Grassmann, Simon; Chaloupka, Michael; Layritz, Patrick; Kruger, Stephan; Ormanns, Steffen; Rataj, Felicitas; Janssen, Klaus-Peter; Endres, Stefan; Anz, David; Kobold, Sebastian
• Is Part Of: Oncoimmunology. Volume 5:Number 3(2016)
• Publication Date: 2016-03-03
• Subjects: Adoptive transfer -- chemokine -- CCL22 -- CCR4 -- LFA-1 -- tumor; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2015.1105428
• Languages: English
• ISSNs: 2162-402X

Abstract

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).