title: Prospects for adoptive immunotherapy of pancreatic cancer using chimeric antigen receptor-engineered T-cells.
abstract: Adoptive immunotherapy using chimeric antigen receptor (CAR) engineered T-cells is emerging as a powerful new approach to cancer immunotherapy. CARs are fusion molecules that couple the antibody-like binding of a native cell surface target to the delivery of a bespoke T-cell activating signal. Recent studies undertaken by several centers have demonstrated highly compelling efficacy in patients with acute and chronic B-cell malignancies. However, comparable therapeutic activity has not been achieved in solid tumors. Modern management of pancreatic ductal adenocarcinoma (PDAC) remains ineffective, reflected in the virtual equivalence of annual incidence and mortality statistics for this tumor type. Increasing evidence indicates that these tumors are recognized by the immune system, but deploy powerful evasion strategies that limit natural immune surveillance and render efforts at immunotherapy challenging. Here, we review preclinical and clinical studies that have been initiated or completed in an effort to develop CAR-based immunotherapy for PDAC. We also consider the hurdles to the effective clinical development of this exciting new therapeutic modality.
authors.affiliation: a Department of Medical Oncology , Guy's and St Thomas' NHS Foundation Trust , London , UK .
authors.forename: Doraid
authors.initials: D
authors.lastname: Alrifai
authors.affiliation: a Department of Medical Oncology , Guy's and St Thomas' NHS Foundation Trust , London , UK .|b Division of Cancer Studies , Department of Research Oncology, King's College London , London , UK .
authors.forename: Debashis
authors.initials: D
authors.lastname: Sarker
authors.affiliation: b Division of Cancer Studies , Department of Research Oncology, King's College London , London , UK .|c Department of Immunology , Barnet Hospital, Royal Free London NHS Foundation Trust , London , UK , and.|d Department of Clinical Immunology and Allergy , King's College Hospital NHS Foundation Trust , London , UK.
authors.forename: John
authors.initials: J
authors.lastname: Maher
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000276:immunology / Q000628:therapy; D005818:Genetic Engineering; D006801:Humans; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000628:therapy; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D011948:Receptors, Antigen, T-Cell
keywords: Chimeric antigen receptor; engineered T-cell; pancreatic ductal adenocarcinoma; tumor-infiltrating lymphocyte