title: Genetically modified T-cell therapy for osteosarcoma.
abstract: T-cell immunotherapy may offer an approach to improve outcomes for patients with osteosarcoma, who fail current therapies. In addition, it has the potential to reduce treatment-related complications for all patients. Generating tumor-specific T cells with conventional antigen presenting cells ex vivo is time consuming and often results in T-cell products with a low frequency of tumor-specific T cells. In addition, the generated T cells remain sensitive to the immunosuppressive tumor microenvironment. Genetic modification of T cells is one strategy to overcome these limitations. For example, T cells can be genetically modified to render them antigen specific, resistant to inhibitory factors, or increase their ability to home to tumor sites. Most genetic modification strategies have only been evaluated in preclinical models, however early phase clinical trials are in progress. In this chapter we review the current status of gene-modified T-cell therapy with special focus on osteosarcoma, highlighting potential antigenic targets, preclinical and clinical studies, and strategies to improve current T-cell therapy approaches.
authors.affiliation: Center for Cell and Gene Therapy, Houston Methodist, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Street, Suite 1770, Houston, TX, 77030, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: DeRenzo
authors.forename: Stephen
authors.initials: S
authors.lastname: Gottschalk
mesh_terms: D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D001859:Bone Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D060846:Cell Engineering; D002986:Clinical Trials as Topic; D015870:Gene Expression; D006801:Humans; D016219:Immunotherapy, Adoptive; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D012516:Osteosarcoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000637:transplantation
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte