An NK cell line (NK92-41BB) expressing high levels of granzyme is engineered to express the high affinity chimeric genes CD16/CAR

Natural killer (NK) cells are known to play a role in mediating innate immunity and have been implicated in mediating anti-tumor responses via antibody-dependent cell-mediated cytotoxicity (ADCC) based on the reactivity of CD16 with the Fc region of human IgG1 antibodies. The NK-92 cell line, devoid of CD16 and derived from a lymphoma patient, has been well characterized. The adoptive transfer of irradiated NK-92 cells demonstrated safety and showed preliminary evidence of clinical benefit for cancer patients. The molecules 41BB and CD3 are commonly used as stimulators in the CAR structure, and their expression in NK cells can promote the activation of NK cells, leading to the enhanced perforin- and granzyme-mediated lysis of tumor cells. This study showed that genetically modified NK-92 cells combined with antibody-mediated ADCC using rituximab and trastuzumab monoclonal antibodies lysed tumor cells more efficient than the NK-92 cell lines. It also showed that the anti-tumor activity of chimeric stimulator molecules of the CAR-modified CD16 receptor was stronger than that of CD16 (allotype V158). These studies provide a rationale for the use of genetically modified NK-92 cells in combination with IgG1 anti-tumor monoclonal antibodies. We also provide a rationale for the chimeric modified CD16 receptor that can improve the anti-tumor effect of NK92 cells via ADCC.

     

泾河流域景观稳定性与类型转换机制

以泾河流域为例研究景观格局的变化.结果表明,泾河流域198～2000年间,景观结构变化不大,以草地景观和耕地景观为主.草地景观和农耕地景观占流域总面积的85%以上,其次为林地景观,约占10%,其他景观类型仅占5%左右,说明流域的宏观景观格局不会在10～20年的时间尺度上发生结构性改变.大流域内景观类型之间可以相互转换,在5年和10年尺度上,主导景观类型的自稳定强度均在89%以上,转换为其他类型的强度在11%以内.不同景观类型组分中,占比例越小的景观类型转换为其他类型或消失的速度越快.同一大类景观类型中的亚景观类型之间相互转换幅度较大.流域内景观特征表现出一定的时空变化规律.从上游到下游,景观特征变化的趋势是优势度、聚集度增加,分维数下降,斑块密度由低到高,再由高到低;在时间尺度上,优势度、聚集度下降,分维数保持稳定,斑块密度增加.自2000年实行草地围封和退耕还林政策以来,泾河流域NDVI低值区由7.4%减至0.8%,NDVI高值区由29.8%减至25.1%,较高值区由18.3%增加到25.7%,最高值区由2.3%增至5.5%,表明该流域景观质量呈现增高趋势.