Chimeric antigen receptor (CAR)-T cell therapy is a transformative treatment against advanced malignancies. Unfortunately, once administrated in vivo, CAR-T cells become out of artificial control, and fierce response to CAR-T therapy may cause severe adverse events, represented by cytokine-release syndrome and on-target/off-tumor effects. Here, a nanomodified switch strategy is developed, leading to sustained and precise "on-tumor only" activation of CAR-T cells. Here, original gelatinase-responsive nanoparticles (NPs) are used to selectively deliver the heterodimerizing switch, which is the key component of switchable CAR with separated activation modules. The "NanoSwitch" is tumor-specific, thus inactivated switchable CAR-T cells do little harm to normal cells, even if the normal cells express the target of CAR-T. Owing to the sustained-release effect of NPs, the CAR-T cells are activated smoothly, avoiding sudden release of cytokine. These data introduce NanoSwitch as a universal and applicable solution to safety problems of CAR-T therapy regardless of the target.

One year following bladder cancer surgery, a 65‐year‐old man had computed tomography (CT) that revealed bilateral pulmonary nodules. Pulmonary wedge resections were performed after the nodules were found to grow in follow‐up. Unusually, we found that these two lesions were not homologous, nor were they metastases from prior bladder cancer, and therefore, synchronous double primary lung cancer (sDPLC) was diagnosed. The immunohistochemical findings excluded the possibility of bladder cancer metastasis, but could not determine whether they were from the same source. Next generation sequencing (NGS) supported the diagnosis sDPLC because they amply demonstrated the two sources’ distinct origins. Finally, after discussion with pathologists, this patient was diagnosed as small cell lung carcinoma (SCLC) and received postoperative EP chemotherapy. We also documented a few rather uncommon alterations that might serve as a foundation for further investigation. This case suggests that in addition to immunohistochemical, NGS is also helpful to clarify the etiology and refine the pathological classification of tumors, which has guiding significance for the establishment of precise diagnosis and optimal treatment.