Chimeric antigen receptor with novel intracellular modules improves antitumor performance of T cells.

The excessive cytokine release and limited persistence represent major challenges for chimeric antigen receptor T (CAR-T) cell therapy in diverse tumors. Conventional CARs employ an intracellular domain (ICD) from the ζ subunit of CD3 as a signaling module, and it is largely unknown how alternative CD3 chains potentially contribute to CAR design. Here, we obtained a series of CAR-T cells against HER2 and mesothelin using a domain comprising a single immunoreceptor tyrosine-based activation motif from different CD3 subunits as the ICD of CARs.

Discovery of a highly potent, selective, and stable d-amino acid-containing peptide inhibitor of CDK9/cyclin T1 interaction for the treatment of prostate cancer.

Cyclin-dependent kinase 9 (CDK9) plays a pivotal role in promoting oncogenic transcriptional pathways, significantly contributing to the development and progression of cancer. Given the unique biostability of d-amino acid, the development of d-amino acid-containing peptides (DAACPs) is a promising strategy for cancer treatment. Currently, no DAACPs inhibitor targeting CDK9-cyclin T1 have been reported.

Aurora kinase B inhibitor AZD1152: repurposing for treatment of lupus nephritis driven by the results of clinical trials.

Background: Lupus nephritis (LN) is one of the most common and severe complications of systemic lupus erythematosus (SLE). Multitarget therapy (MT) achieves a 20% higher complete remission (CR) rate compared to conventional therapy in LN management. Intrigued by its excellent clinical efficacy, we aimed to develop a single-agent therapy with comparable efficacy to MT, offering a simplified treatment regimen.

Characterization of a novel conditional knockout mouse model to assess efficacy of mRNA therapy in the context of severe ornithine transcarbamylase deficiency.

Ornithine transcarbamylase deficiency (OTCD) is the most common urea cycle disorder, characterized by hyperammonemia and accompanied by a high unmet patient need. mRNA therapies have been shown to be efficacious in hypomorphic Sparse-fur abnormal skin and hair (Spf-ash) mice, a model of late-onset disease. However, studying the efficacy of ornithine transcarbamylase (OTC) mRNA therapy in traditional knockout mice, a model for severe early-onset OTCD, is hampered by the rapid lethality of the model, and poor lipid nanoparticle (LNP) uptake into neonatal mouse liver.

Intelligent Optimization Design Framework for Alternating Current Pulse Modulation Electrohydrodynamic Printing Process Parameters.

To achieve efficient size tuning of printed microstructures on insulating substrates, an integrated process parameter intelligent optimization design framework for alternating current pulse modulation electrohydrodynamic (AC-EHD) printing is proposed for the first time. The framework is comprised of two stages: the construction of a prediction model and the acquisition of process parameters. The first stage employs the elk herd optimizer(EHO)-artificial neural network(ANN) to establish a mapping relationship between printing process parameters and the size of deposited droplets.