Preclinical evaluation of cyclophosphamide and fludarabine combined with CD19 CAR-T in the treatment of B-cell hematologic malignancies in vivo

Background:Chimeric antigen receptor T(CAR-T)cell therapy has achieved marked therapeutic success in ameliorating hematological malignancies.However,there is an extant void in the clinical guidelines concerning the most effective chemotherapy regimen prior to chimeric antigen receptor T(CAR-T)cell therapy,as well as the optimal timing for CAR-T cell infusion post-chemotherapy.Materials and Methods:We employed cell-derived tumor xenograft(CDX)murine models to delineate the optimal pre-conditioning chemotherapy regimen and timing for CAR-T cell treatment.Furthermore,transcriptome sequencing was implemented to identify the therapeutic targets and elucidate the underlying mechanisms governing the treatment regimen.Results:Our preclinical in vivo evaluation determined that a combination of cyclophosphamide and fludarabine,followed by the infusion of CD19 CAR-T cells five days subsequent to the chemotherapy,exerts the most efficacious therapeutic effect in B-cell hematological malignancies.Concurrently,RNA-seq data indicated that the therapeutic efficacy predominantly perturbs tumor cell metabolism,primarily through the inhibition of key mitochondrial targets,such as C-Jun Kinase enzyme(C-JUN).Conclusion:In summary,the present study offers critical clinical guidance and serves as an authoritative reference for the deployment of CD19 CAR-T cell therapy in the treatment of B-cell hematological malignancies.

Ultralow cross talk arrayed waveguide grating integrated with tunable microring filter array

The silicon-based arrayed waveguide grating(AWG)is widely used due to its compact footprint and its compatibility with the mature CMOS process.However,except for AWGs with ridged waveguides of a few micrometers of cross section,any small process error will cause a large phase deviation in other AWGs,resulting in an increasing cross talk.In this paper,an ultralow cross talk AWG via a tunable microring resonator(MRR)filter is demonstrated on the SOI platform.The measured insertion loss and minimum adjacent cross talk of the designed AWG are approximately 3.2 and-45.1 d B,respectively.Compared with conventional AWG,its cross talk is greatly reduced.

Stereopure AIMer:A Promising RNA Base-editing Tool for Monogenic Neurological Diseases

The continuous development of various gene therapies has brought new light to the treatment of genetic diseases.Among them,therapies targeting monogenic diseases are relatively progressive and promising due to the explicit and clear pathogenesis.The discovery and development of clustered regularly interspaced short palindromic repeats/associated nuclease(CRISPR/Cas)and related technologies was undoubtedly an extraordinary leap forward for gene therapy.