Adoptive cell transfer therapy for hepatocellular carcinoma / 医学前沿

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. This malignancy is associated with poor prognosis and high mortality. Novel approaches for prolonging the overall survival of patients with advanced HCC are urgently needed. The antitumor activities of adoptive cell transfer therapy (ACT), such as strategies based on tumor-infiltrating lymphocytes and cytokine-induced killer cells, are more effective than those of traditional strategies. Currently, chimeric antigen receptor T-cell (CAR-T) immunotherapy has achieved numerous breakthroughs in the treatment of hematological malignancies, including relapsed or refractory lymphoblastic leukemia and refractory large B-cell lymphoma. Nevertheless, this approach only provides a modest benefit in the treatment of solid tumors. The clinical results of CAR-T immunotherapy for HCC that could be obtained at present are limited. Some published studies have demonstrated that CAR-T could inhibit tumor growth and cause severe side effects. In this review, we summarized the current application of ACT, the challenges encountered by CAR-T technology in HCC treatment, and some possible strategies for the future direction of immunotherapeutic research.

Chimeric antigen receptor T cell targeting EGFRvIII for metastatic lung cancer therapy / 医学前沿

Lung cancer is the most common incident cancer and the leading cause of cancer death. In recent years, the development of tumor immunotherapy especially chimeric antigen receptor T (CAR-T) cell has shown a promising future. Epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific mutation expressed in various types of tumors and has been detected in non-small cell lung cancer with a mutation rate of 10%. Thus, EGFRvIII is a potential antigen for targeted lung cancer therapy. In this study, CAR vectors were constructed and transfected into virus-packaging cells. Then, activated T cells were infected with retrovirus harvested from stable virus-producing single clone cell lines. CAR expression on the surfaces of the T cells was detected by flow cytometry and Western blot. The function of CAR-T targeting EGFRvIII was then evaluated. The EGFRvIII-CAR vector was successfully constructed and confirmed by DNA sequencing. A stable virus-producing cell line was produced from a single clone by limited dilution. The culture conditions for the cell line, including cell density, temperature, and culture medium were optimized. After infection with retrovirus, CAR was expressed on more than 90% of the T cells. The proliferation of CAR-T cells were induced by cytokine and specific antigen in vitro. More importantly, EGFRvIII-CART specifically and efficiently recognized and killed A549-EGFRvIII cells with an effector/target ratio of 10:1 by expressing and releasing cytokines, including perforin, granzyme B, IFN-γ, and TNF-α. The in vivo study indicated that the metastasis of A549-EGFRvIII cells in mice were inhibited by EGFRvIII-CART cells, and the survival of the mice was significantly prolonged with no serious side effects. EGFRvIII-CART showed significantly efficient antitumor activity against lung cancer cells expressing EGFRvIII in vivo and in vitro. Therefore, CAR-T targeting EGFRvIII is a potential therapeutic strategy in preventing recurrence and metastasis of lung cancer after surgery.

Significance of computed tomography in morphological classification of blunt traumatic thoracic aortic injury / 中华创伤杂志

Objective To discuss imaging classification of blunt traumatic thoracic aortic injury (BTTAI) and weigh guideline value of its imaging classification to surgical options.Methods BTTAI in 12 patients were divided into three types in accordance with outline of aortic injury revealed by CT imaging,i.e.,type A of normal outline of aortic blood vessel but free endothelium in aortic cavity,type B of abnormal aortic outline and contrast extravasation to aortic lumen exterior but only confining to mediastina,and type C of abnormal aortic outline and contrast leakage to thoracic cavity.Significance of BTTAI morphological classification was analyzed according to data,such as systemic injury severity score (ISS),local injury sites,surgical approaches and patients' outcome.Results Multiple injuries combined with BTTAI were observed in all patients whose aortic lesion image could be all generalized by above-mentioned classification.BTTAI image showed type A in three patients,type B in seven and type C in two.Pseudoaneurysm was confirmed as the foremost common BTTAI.There were no significant differences in ISS,hypotension morbidity,treatment methods or mortality between each type of BTTAI.Conclusions BTTAI occurs mostly in multiple injuries and thus overall injury severity assessment is not only depended on aortic lesion classification.BTTAI classification in this study reflects injury severity of vessel wall,takes account to location of lesion and adjacent relations (especially length of landing zone) and hence has accurate referential value for surgical decisions.