title: The Evolution of T-cell Therapies for Solid Malignancies.
abstract: Primary resistant, recurrent, and relapsed solid tumors are often nonresponsive to conventional antineoplastic therapies. Moreover, in responsive tumors, the therapeutic-to-toxic range of these interventions remains quite narrow, such that side effects of therapy are substantial. Targeted therapies, such as adoptive T-cell transfer, not only spare normal tissues but also use alternative killing mechanisms to which the tumor cells are usually not immune. Adoptive T-cell transfer for solid tumors faces unique challenges because of the inherent heterogeneity of tumor parenchyma, the complexity of the tumor microenvironment, and tumor occurrence in areas with limited therapeutic accessibility. In this review, we examine the recent evolution of various T-cell-based immunotherapeutics, the mechanisms of action behind their antitumor activity, their increasing complexity, and the prospect of building on previous successes in the treatment of solid tumors.
authors.affiliation: Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, Texas. Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, and Houston Methodist Hospital, Houston, Texas. Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas. Department of Pediatrics, Baylor College of Medicine, Houston, Texas. nahmed@bcm.edu fousek@bcm.edu.
authors.forename: Kristen
authors.initials: K
authors.lastname: Fousek
authors.affiliation: Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, Texas. Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, and Houston Methodist Hospital, Houston, Texas. Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas. Department of Pediatrics, Baylor College of Medicine, Houston, Texas. nahmed@bcm.edu fousek@bcm.edu.
authors.forename: Nabil
authors.initials: N
authors.lastname: Ahmed
mesh_terms: D019264:Adoptive Transfer; D019008:Drug Resistance, Neoplasm / Q000235:genetics / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D059016:Tumor Microenvironment / Q000276:immunology