In this March 2025 issue of Translational Lung Cancer Research, a pioneering study, led by Professor Shuben Li from the First Affiliated Hospital of Guangzhou Medical University, presents compelling evidence demonstrating the efficacy, accuracy and safety of electromagnetic navigation bronchoscopy-guided dye marking (ENBDM).

The article entitled "A better option for localization of multiple pulmonary nodules in the ipsilateral lung: electromagnetic navigation bronchoscopyguided preoperative localizationl". This retrospective study compared ENBDM with conventional CT-guided percutaneous lung puncture (CTPLP) in 203 patients undergoing thoracoscopic surgery between 2018 and 2023, supporting ENBDM as an optimal strategy for localizing multiple ipsilateral lung nodules.

Researchers present a new method to safely and preferentially generate CAR T cells directly inside the body using targeted lipid nanoparticles that deliver mRNA directly to T cells. The approach showed rapid and sustained immune reprogramming in preclinical models, highlighting its promise for treating cancer and autoimmune diseases. Adoptive immunotherapy, which harnesses a patient’s own immune cells to treat disease, holds immense therapeutic potential. Among its most prominent forms is CAR T cell therapy, in which T cells are genetically engineered to recognize and attack tumor cells. However, because CAR T cells are generated outside the body, these therapies are complex, costly, and dependent on specialized medical infrastructure. To overcome the hurdles of traditional CAR T cell therapies, Theresa Hunter and colleagues developed a new strategy for generating CAR T cells directly inside the body using targeted lipid nanoparticles (tLNPs) that carry a desired mRNA cargo. The use of mRNA in this approach should avoid the risk of permanent genetic alteration because, unlike DNA-based methods, mRNA does not integrate into the T cell genome.

A major obstacle in delivering mRNA with lipid nanoparticles (LNPs), however, is their tendency to be absorbed by the liver’s reticuloendothelial system, which filters out foreign particles from the bloodstream. To address this, Hunter et al. designed a specialized ionizable lipid (L829) and used it to create LNPs targeted to CD5, a protein found on T cells. When tested in mice, rats, and cynomolgus monkeys, these CD5-L829-tLNPs showed reduced liver uptake and more precise delivery to T cells, demonstrating improved targeting and biodistribution. To evaluate the efficacy of the system, the authors used blood samples from humans with autoimmune disease and showed that patient-derived T cells could be engineered with similar efficiency to those from healthy donors and that they could successfully eliminate the patients’ B cells. In mouse models engrafted with human immune cells, a single dose of the tLNPs led to rapid, targeted B cell depletion within hours, with effects lasting up to two weeks. In a leukemia xenograft experimental model, repeated dosing of the tLNPs produced near-complete tumor clearance, underscoring the potential of this in vivo approach for treating both cancer and autoimmune conditions.