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Objectives: Recent studies have identified expression of the non‐functional P2X7 (nfP2X7) receptor on various malignant cells including ovarian cancer, but not on normal cells, which makes it a promising tumour‐associated antigen candidate for chimeric antigen receptor (CAR)‐T‐cell immunotherapies. In this study, we assessed the cytotoxic effects of nfP2X7‐CAR‐T cells on ovarian cancer using in vitro and in vivo models. Methods: We evaluated the effects of nfP2X7‐CAR‐T cells on ovarian cancer cell lines (SKOV‐3, OVCAR3, OVCAR5), normal peritoneal cells (LP‐9) and primary serous ovarian cancer cells derived from patient ascites in vitro using monolayer and 3D spheroid assays. We also evaluated the effects of nfP2X7‐CAR‐T cells on patient‐derived tissue explants, which recapitulate an intact tumour microenvironment. In addition, we investigated the effect of nfP2X7‐CAR‐T cells in vivo using the OVCAR‐3 xenograft model in NOD‐scid IL2Rγnull (NSG) mice. Results: Our study found that nfP2X7‐CAR‐T cells were cytotoxic and significantly inhibited survival of OVCAR3, OVCAR5 and primary serous ovarian cancer cells compared with un‐transduced CD3+ T cells in vitro. However, no significant effects of nfP2X7‐CAR‐T cells were observed for SKOV3 or normal peritoneal cells (LP‐9) cells with low P2X7 receptor expression. Treatment with nfP2X7‐CAR‐T cells increased apoptosis compared with un‐transduced T cells in patient‐derived explants and correlated with CD3 positivity. Treatment with nfP2X7‐CAR‐T cells significantly reduced OVCAR3 tumour burden in mice compared with un‐transduced CD3 cells for 7–8 weeks. Conclusion: This study demonstrates that nfP2X7‐CAR‐T cells have great potential to be developed as a novel immunotherapy for ovarian cancer. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T (CAR‐T) cell therapy is rapidly becoming a frontline cancer therapy. However, the manufacturing process is time‐, labor‐ and cost‐intensive, and it suffers from significant bottlenecks. Many CAR‐T products fail to reach the viability release criteria set by regulators for commercial cell therapy products. This results in non‐recoupable costs for the manufacturer and is detrimental to patients who may not receive their scheduled treatment or receive out‐of‐specification suboptimal formulation. It is demonstrated here that inertial microfluidics can, within minutes, efficiently deplete nonviable cells from low‐viability CAR‐T cell products. The percentage of viable cells increases from 40% (SD ± 0.12) to 71% (SD ± 0.09) for untransduced T cells and from 51% (SD ± 0.12) to 71% (SD ± 0.09) for CAR‐T cells, which meets the clinical trials' release parameters. In addition, the processing of CAR‐T cells formulated in CryStor yields a 91% reduction in the amount of the cryoprotectant dimethyl sulfoxide. Inertial microfluidic processing has no detrimental effects on the proliferation and cytotoxicity of CAR‐T cells. Interestingly, ≈50% of T‐regulatory and T‐suppressor cells are depleted, suggesting the potential for inertial microfluidic processing to tune the phenotypical composition of T‐cell products. [ABSTRACT FROM AUTHOR]

Research has been conducted on filamentous actinobacteria from the surface-sterilized roots of wheat plants. The authors describe the isolation, identification and characterization of these bacteria, and discuss bacteria's role in pathogen defence and growth regulation of their hosts.

Research shows that endophytic colonization of Streptomyces species occurs in a very early stage of wheat seed development. Data reveal that bacterial colonization is seen in the embryo, endosperm, and emerging radicle of the wheat seed.

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Presents a letter responding to a query about actinobacteria in plant roots.