Spinal Cord Stimulation for Poststroke Hemiparesis: A Scoping Review.

IMPORTANCE: Spinal cord stimulation (SCS) is a neuromodulation technique that can improve paresis in individuals with spinal cord injury. SCS is emerging as a technique that can address upper and lower limb hemiparesis. Little is understood about its effectiveness with the poststroke population. OBJECTIVE: To summarize the evidence for SCS after stroke and any changes in upper extremity and lower extremity motor function. DATA SOURCES: PubMed, Web of Science, Embase, and CINAHL. The reviewers used hand searches and reference searches of retrieved articles. There were no limitations regarding publication year. STUDY SELECTION AND DATA COLLECTION: This review followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. The inclusion and exclusion criteria included a broad range of study characteristics. Studies were excluded if the intervention did not meet the definition of SCS intervention, used only animals or healthy participants, did not address upper or lower limb motor function, or examined neurological conditions other than stroke. FINDINGS: Fourteen articles met the criteria for this review. Seven studies found a significant improvement in motor function in groups receiving SCS. CONCLUSIONS AND RELEVANCE: Results indicate that SCS may provide an alternative means to improve motor function in the poststroke population. Plain-Language Summary: The results of this study show that spinal cord stimulation may provide an alternative way to improve motor function after stroke. Previous neuromodulation methods have targeted the impaired supraspinal circuitry after stroke. Although downregulated, spinal cord circuitry is largely intact and offers new possibilities for motor recovery.

Chimeric antigen receptor T cells to target CD79b in B-cell lymphomas.

BACKGROUND: Chimeric antigen receptor (CAR) T cells targeting CD19 mediate potent and durable effects in B-cell malignancies. However, antigen loss or downregulation is a frequent cause of resistance. Here, we report development of a novel CAR T-cell therapy product to target CD79b, a pan B-cell antigen, widely expressed in most B-cell lymphomas. METHODS: We generated a novel anti-CD79b monoclonal antibody by hybridoma method. The specificity of the antibody was determined by testing against isogenic cell lines with human CD79b knock-in or knock-out. A single-chain variable fragment derived from the monoclonal antibody was used to make a panel of CD79b-targeting CAR molecules containing various hinge, transmembrane, and co-stimulatory domains. These were lentivirally transduced into primary T cells and tested for antitumor activity in in vitro and in vivo B-cell lymphoma models. RESULTS: We found that the novel anti-CD79b monoclonal antibody was highly specific and bound only to human CD79b and no other cell surface protein. In testing the various CD79b-targeting CAR molecules, superior antitumor efficacy in vitro and in vivo was found for a CAR consisting CD8α hinge and transmembrane domains, an OX40 co-stimulatory domain, and a CD3ζ signaling domain. This CD79b CAR specifically recognized human CD79b-expressing lymphoma cell lines but not CD79b knock-out cell lines. CD79b CAR T cells, generated from T cells from either healthy donors or patients with lymphoma, proliferated, produced cytokines, degranulated, and exhibited robust cytotoxic activity in vitro against CD19+ and CD19- lymphoma cell lines and patient-derived lymphoma tumors relapsing after prior CD19 CAR T-cell therapy. Furthermore, CD79b CAR T cells were highly efficient at eradicating pre-established lymphoma tumors in vivo in three aggressive lymphoma xenograft models, including two cell line-derived xenografts and one patient-derived xenograft. Notably, these CAR T cells did not demonstrate any significant tonic signaling activity or markers of exhaustion. CONCLUSION: Our results indicated that this novel CD79b CAR T-cell therapy product has robust antitumor activity against B-cell lymphomas. These results supported initiation of a phase 1 clinical trial to evaluate this product in patients with relapsed or refractory B-cell lymphomas.