Deep‐MSIM: Fast Image Reconstruction with Deep Learning in Multifocal Structured Illumination Microscopy

Abstract Fast and precise reconstruction algorithm is desired for for multifocal structured illumination microscopy (MSIM) to obtain the super‐resolution image. This work proposes a deep convolutional neural network (CNN) to learn a direct mapping from raw MSIM images to super‐resolution image, which takes advantage of the computational advances of deep learning to accelerate the reconstruction. The method is validated on diverse biological structures and in vivo imaging of zebrafish at a depth of 100 µm. The results show that high‐quality, super‐resolution images can be reconstructed in one‐third of the runtime consumed by conventional MSIM method, without compromising spatial resolution. Last but not least, a fourfold reduction in the number of raw images required for reconstruction is achieved by using the same network architecture, yet with different training data

Novel CD19-specific γ/δ TCR-T cells in relapsed or refractory diffuse large B-cell lymphoma

Abstract Background T cell receptor (TCR)-T cells possess similar effector function, but milder and more durable signal activation compared with chimeric antigen receptor-T cells. TCR-T cell therapy is another active field of cellular immunotherapy for cancer. Methods We previously developed a human anti-CD19 antibody (ET190L1) and generated novel CD19-specific γ/δ TCR-T cells, ET019003, by fusing the Fab fragment of ET190L1 with γ/δ TCR constant chain plus adding an ET190L1-scFv/CD28 co-stimulatory molecule. ET019003 cells were tested in preclinical studies followed by a phase 1 clinical trial. Results ET019003 cells produced less cytokines but retained comparable antitumor potency than ET190L1-CAR-T cells in vivo and in vitro. In the first-in-human trial, eight patients with relapsed or refractory DLBCL were treated. CRS of grade 1 was observed in three (37.5%) patients; ICANS of grade 3 was noted in one (12.5%) patient. Elevation of serum cytokines after ET019003 infusion was almost modest. With a median follow-up of 34 (range 6–38) months, seven (87.5%) patients attained clinical responses and six (75%) achieved complete responses (CR). OS, PFS and DOR at 3 years were 75.0%, 62.5%, and 71.4%, respectively. Notably, patient 1 with primary CNS lymphoma did not experience CRS or ICANS and got an ongoing CR for over 3 years after infusion, with detectable ET019003 cells in CSF. ET019003 showed striking in vivo expansion and persisted in 50% of patients at 12 months. Three patients received a second infusion, one for consolidation therapy after CR and two for salvage therapy after disease progression, but no response was observed. ET019003 expansion was striking in the first infusion, but poor in the second infusion. Conclusions CD19-specific γ/δ TCR-T cells, ET019003, had a good safety profile and could induce rapid responses and durable CR in patients with relapsed or refractory DLBCL, even primary CNS lymphoma, presenting a novel and potent therapeutic option for these patients. Trial registration: NCT04014894