Rat Anti-Mouse CD19 monoclonal antibody, clone 2E4

T cells are central to all currently effective cancer immunotherapies, but the characteristics defining therapeutically effective anti-tumor T cells have not been comprehensively elucidated. Here, we delineate four phenotypic qualities of effective anti-tumor T cells: cell expansion, differentiation, oxidative stress, and genomic stress. Using a CRISPR-Cas9-based genetic screen of primary T cells we measured the multi-phenotypic impact of disrupting 25 T cell receptor-driven kinases. We identified p38 kinase as a central regulator of all four phenotypes and uncovered transcriptional and antioxidant pathways regulated by p38 in T cells. Pharmacological inhibition of p38 improved the efficacy of mouse anti-tumor T cells and enhanced the functionalities of human tumor-reactive and gene-engineered T cells, paving the way for clinically relevant interventions.

Two potentially related microRNAs (miRNAs; miR-150-5p and miR-146a-5p) were examined after low-dose rituximab (RTX) treatment in patients with acetylcholine receptor antibody (AChR)-positive refractory myasthenia gravis (MG). In this prospective, open-label, and self-controlled pilot trial, 12 AChR-positive refractory MG patients were administrated a single, low dose of RTX and followed up at six months. Results showed that RTX decreased the serum exosomal miR-150-5p, scores on three clinical indices (MGFA, MMT, ADL), and patients' prednisolone requirement. Additionally, CD19 + and CD27+ B cells decreased, showing a strong correlation with miR-150-5p. In conclusion, low-dose RTX is effective for AChR-positive refractory MG treatment. Furthermore, our data support the role of miR-150-5p as a potential biomarker for MG.