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Advanced gene transfer technologies and profound immunological insights have enabled substantial increases in the efficacy of anticancer adoptive cellular therapy (ACT). In recent years, the U.S. Food and Drug Administration and European Medicines Agency have approved six engineered T cell therapeutic products, all chimeric antigen receptor-engineered T cells directed against B cell malignancies. Despite encouraging clinical results, engineered T cell therapy is still constrained by challenges, which could be addressed by genome editing. As RNA-guided Clustered Regularly Interspaced Short Palindromic Repeats technology passes its 10-year anniversary, we review emerging applications of genome editing approaches designed to (1) overcome resistance to therapy, including cancer immune evasion mechanisms; (2) avoid unwanted immune reactions related to allogeneic T cell products; (3) increase fitness, expansion capacity, persistence, and potency of engineered T cells, while preserving their safety profile; and (4) improve the ability of therapeutic cells to resist immunosuppressive signals active in the tumor microenvironment. Overall, these innovative approaches should widen the safe and effective use of ACT to larger number of patients affected by cancer.

Purpose: In Japan, gene therapy and cellular therapy are categorized as regenerative medicine products based on the Pharmaceuticals and Medical Devices Law that was implemented in 2014. In this new law, regenerative medicine products were newly defined, and a conditional and term-limited approval system for regenerative medicine products was instituted. In addition, the Ministry of Health, Labour and Welfare instituted the SAKIGAKE (meaning pioneer or forerunner in Japanese) designation system in 2015. This designation is similar to the breakthrough therapy designation in the United States. These new regulatory frameworks have stimulated clinical development of new gene and cellular products in Japan. In fact, oncolytic virus therapy for glioblastoma and NY-ESO-1 (T-cell receptor) T-cell therapy for synovial sarcoma were granted SAKIGAKE designation in 2016 and 2018, respectively. Oncolytic virus therapy and genetically engineered T-cell therapy for cancer are being actively developed and examined in investigator-initiated trials., Methods: This review analyzes the domestic and international clinical trial registries to comprehensively collect information on clinical trials of gene and cellular therapeutic products for cancer in Japan., Implications: Current trends in clinical development of gene and cellular therapeutic products for cancer in Japan are discussed., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Driving with upper extremity immobilization can be potentially dangerous. The aim of this article is to review current medical literature, state laws, and guidelines on driving with upper extremity immobilization and appraise the available evidence. A literature search was conducted to identify citations related to driving with upper extremity immobilization and included a law literature search. Each state's Department of Motor Vehicle handbook was reviewed. Fourteen studies were reviewed and 5 provided subjective and/or objective assessments of upper limb immobilization. Of 2 studies that evaluated only below-elbow immobilization, 1 found driving in a wrist splint had no perceptible effect on driving ability, and the other supported safe driving under normal conditions. The studies that evaluated both below- and above-elbow immobilization recommended against driving with left arm above-elbow immobilization. Two of them found a trend toward worse driving performance in both below- and above-elbow splints. The following organizations' policies on driving are (1) The American Medical Association and National Highway Traffic Association have a joint recommendation for older drivers recommending referral to a rehabilitation specialist, (2) the U.S. Public Health Service recommends normal motor function and adequate mobility of both upper extremities and a performance examination when impaired, and (3) the U.S. Department of Transportation recommends a performance evaluation to determine fitness of commercial motor vehicle drivers. There are no state statutes or multijurisdictional surveys on the topic. This review finds that driving is hindered in some splints, there are substantial variations in physician practice patterns, there are no formal guidelines for physicians and patients to consider, and there is a paucity of published literature on this topic in the United States. Both physicians and patients would benefit from evidence-based recommendations or practice guidelines., (Copyright © 2015 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)