In Synergy: Optimizing CAR T Development and Personalizing Patient Care Using Single-Cell Technologies.

Chimeric antigen receptor (CAR) T therapies hold immense promise to revolutionize cancer treatment. Nevertheless, key challenges, primarily in solid tumor settings, continue to hinder the application of this technology. Understanding CAR T-cell mechanism of action, in vivo activity, and clinical implications is essential for harnessing its full therapeutic potential. Single-cell genomics and cell engineering tools are becoming increasingly effective for the comprehensive research of complex biological systems. The convergence of these two technologies can accelerate CAR T-cell development. Here, we examine the potential of applying single-cell multiomics for the development of next-generation CAR T-cell therapies. SIGNIFICANCE: Although CAR T-cell therapies have demonstrated remarkable clinical results in treating cancer, their effectiveness in most patients and tumor types remains limited. Single-cell technologies, which are transforming our understanding of molecular biology, provide new opportunities to overcome the challenges of CAR T-cell therapies. Given the potential of CAR T-cell therapy to tip the balance in the fight against cancer, it is important to understand how single-cell multiomic approaches can be leveraged to develop the next generations of more effective and less toxic CAR T-cell products and to provide powerful decision-making tools for clinicians to optimize treatment and improve patient outcomes.

The industrial genomic revolution: A new era in neuroimmunology.

Recent discoveries have highlighted the importance of understanding the complex interactions between the brain and immune systems in health and neurodegenerative disease. In this Primer, we outline single-cell multiomics approaches. Applied to patient samples with rich metadata, functional organoids, and animal models, single-cell studies will facilitate the next big leap in translational neuro-immune research. We believe this will pave the way for reshaping our understanding of the neuro-immune interplay: from descriptive to functional, from broad cell types to effective pathways, spatial organization, biomarkers, and targets, toward a comprehensive mechanistic understanding that will be the impetus for drug discovery and therapeutic breakthroughs. We envision that in the near future, single-cell multiomics technologies, along with the advances in immunotherapy development, will become a major driving force and fully integrated resource in the toolset for the development of therapeutic agents in neuroimmunology, which will revolutionize drug development for treating neurodegenerative diseases.

The validity and reliability of the OneStep smartphone application under various gait conditions in healthy adults with feasibility in clinical practice.

OBJECTIVE: Primary purpose of this study was to determine the validity and reliability of the OneStep smartphone application in healthy adults. Secondary purpose was to determine the feasibility of measuring gait dysfunction, limitation in spatiotemporal characteristics, longitudinally in patients following total hip or knee arthroplasty. METHODS: First objective, 20 healthy adults (mean age, 42.3 ± 19.7 years; 60% males; mean body mass index, 29.0 ± 5.2 kg/m2) underwent gait analysis under four gait conditions (self-selected gait speed, fixed gait speed at 0.8 m/s, fixed gait speed at 2.0 m/s and self-selected gait speed with dual task) for the validity and reliability of the smartphone to the motion laboratory. Reliability was determined by intraclass correlation coefficients. Validity was determined by Pearson correlations. Agreement was assessed by the Bland-Altman method. Second objective, 12 additional patients with total hip or knee arthroplasty (mean age, 58.7 ± 6.5 years; 58% males; mean body mass index, 28.9 ± 5.8 kg/m2) were measured at 2- and 10 weeks postoperatively. The smartphone application was used to evaluate change in gait dysfunction over time within the patients' own environment using paired t test. RESULTS: The smartphone application demonstrated moderate-to-excellent intraclass correlation coefficients for reliability between-system (ICC range, 0.56-0.99), -limb (ICC range, 0.62-0.99) and -device (ICC range, 0.61-0.96) for gait analysis of healthy adults. Pearson correlations were low-to-very high between methods (r range, 0.45-0.99). Bland-Altman analysis revealed relative underestimation of spatiotemporal variables by the smartphone application compared to the motion system. For patients following total hip or knee arthroplasty, gait analysis using the OneStep application demonstrated significant improvement (p < 0.001, Cohen's d > 0.95) in gait dysfunction between 2- and 10 weeks postoperatively. CONCLUSION: The smartphone application can be a valid, reliable and feasible alternative to motion laboratories in evaluating deficits in gait dysfunction in various environments and clinical settings.