title: TCR-engineered T cells to treat tumors: Seeing but not touching?
abstract: Adoptive transfer of T cells gene-engineered with T cell receptors (TCRs) has proven its feasibility and therapeutic potential in the treatment of malignant tumors. To ensure further clinical development of TCR gene therapy, it is necessary to accurately select TCRs that demonstrate antigen-selective responses that are restricted to tumor cells and, at the same time, include strategies that restore or enhance the entry, migration and local accumulation of T cells in tumor tissues. Here, we present the current standing of TCR-engineered T cell therapy, discuss and propose procedures to select TCRs as well as strategies to sensitize the tumor to T cell trafficking, and provide a rationale for combination therapies with TCR-engineered T cells.
authors.affiliation: Laboratory of Tumor Immunology, Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands. Electronic address: j.debets@erasmusmc.nl.
authors.forename: Reno
authors.initials: R
authors.lastname: Debets
authors.affiliation: Inserm U1016, Institut Cochin, Paris, France; CNRS UMR8104, Paris, France; Université Paris Descartes, Paris, France; Equipe Labellisée Ligue Contre le Cancer, Paris, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Donnadieu
authors.affiliation: INSERM U1186, Equipe Labellisée Ligue Contre le Cancer, Gustave Roussy Campus, Villejuif, France.
authors.forename: Salem
authors.initials: S
authors.lastname: Chouaib
authors.affiliation: Department of Oncology, University Hospital of Lausanne (CHUV), University of Lausanne, Switzerland.
authors.forename: George
authors.initials: G
authors.lastname: Coukos
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D019496:Cancer Vaccines / Q000276:immunology*; D002465:Cell Movement; D015316:Genetic Therapy; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D037182:T-Cell Antigen Receptor Specificity; D059016:Tumor Microenvironment
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins
keywords: Antigen recognition; Immune evasion; T cell; T cell receptor; T cell trafficking; Tumor micro-environment