1.National Intellectual Property Administration, Beijing 100088, China;
2.Ministry of Education, Key Laboratory of Protein Science, School of Pharmacy, Tsinghua University, Beijing 100084, China
Abstract：Objective To reveal the research progress of CAR-NK cell therapy from the perspective of patents, in order to provide useful references for further research of innovative entities in our country. Methods CAR-NK related patents are searched through the database of China Patent Search and Service System, and the development trend, regional distribution and the research and development route of main applicants in the field were analyzed. Results The number of CAR-NK patent applications was growing steadily. At present, many domestic and foreign companies were accelerating their deployment in this field. The research of domestic companies mainly focused on the design of CAR-NK with different targets, and involves less combination drugs and upstream and downstream technologies. The technical direction of patent application distribution was relatively simple and was in the relatively initial stage of research and development, while the patent applications of foreign large pharmaceutical companies, focused on multi-angle layout, involving all aspects of the industrial chain. Conclusion The number of high-value patents in the field of CAR-NK in our country is relatively small, and more attention needs to be paid to patent layout and achievement transformation in the future.
[1] 付顺利，刘永军，张娜.肿瘤免疫治疗中NK细胞的激活策略及研究进展[J].生命的化学，2021，41（3）：444-451.
[2] 杨春媚，张婷婷，钱程，等.NK细胞抗肿瘤机制及相关免疫疗法的研究进展[J].中国药理学通报，2019，35（11）：1492-1496.
[3] 张淑芬，曾颖萍，孟廷廷，等.NK细胞的抗肿瘤机制及其在肿瘤靶向治疗中的应用研究进展[J].药学学报，2022， 57（1）：122-133.
[4] 钱开诚，葛四海，揭冯进，等.一种体外活化扩增人NK细胞新方法的建立[J].中国实验血液学杂志，2020，28（5）：1769-1773.
[5] 张可，方珏敏，杨娟，等.异体NK细胞治疗消化道恶性腹水的安全性与疗效（附3例）[J].现代肿瘤医学，2022，30（4）：646-651.
[6] 刘欣，赵娜.CAR-NK细胞在肿瘤免疫学治疗中的应用[J].免疫学杂志，2020，36（4）：358-363.
[7] Liu E，Marin D，Banerjee P，et al. Use of CAR-transduced natural killer cells in CD19-positive lymphoid tumors [J]. N Engl J Med，2020，382（6）：545-553.
[8] Weinkove R，George P，Dasyam N，et al. Selecting costimulatory domains for chimeric antigen receptors：functional and clinical considerations [J]. Clin Transl Immunol，2019，8（5）： e1049.
[9] Lin C，Zhang J. Reformation in chimeric antigen receptor ba- sed cancer immunotherapy：redirecting natural killer cell [J]. Biochem Biophys Acta Rev Cancer，2018，1869（2）：200- 215.
[10] Xiao L，Cen D，Gan H，et al. Adoptive transfer of NKG2D CAR mRNA-engineered natural killer cells in colorectal cancer patients [J]. Mol Ther，2019，27（6）：1114-1125.
[11] Stirrups R. CAR T-cell therapy in refractory large B-cell lymphoma [J]. Lancet Oncol，2018，19（1）：e19.
[12] Ruella M，Xu J，Barrett DM，et al. Induction of resistance to chimeric antigen receptor T cell therapy by transduction of a single leukemic B cell [J]. Nat Med，2018，24（10）：1499- 1503.
[13] Yu M，Luo H，Fan M，et al. Development of GPC3-specific chimeric antigen receptor-engineered natural cells for the treatment of hepatocellular carcinoma [J]. Mol Ther，2017， 26（2）：366-378.
[14] Murakami T，Nakazawa T，Natsume A，et al. Novel human NK cell line carrying CAR targeting EGFRvⅢ induces antitumor effects in glioblastoma cells [J]. Anti-cancer Res，2018，38（9）：5049-5056.
[15] Shah N，Martin-Antonio B，Yang H，et al. Antigen presenting cell-mediated expansion of human umbilical cord blood yields log-scale expansion of natural killer cells with anti-myeloma activity [J]. PLoS One，2013，8（10）：e76781- e76789.
[16] Ni Z，Knorr D，Bendzick L，et al. Expression of chimeric receptor CD4ζ by natural killer cells derived from human pluripotent stem cells improves in vitro activity but does not enhance suppression of HIV infection in vivo [J]. Stem Cells， 2014，32（4）：1021-1031.
[17] Tang X，Yang L，Li Z，et al. First-in-man clinical trail of CAR NK-92 cells safety test of CD33-CAR NK-92 cells in patients with relapsed and refractory acute myeloid leuke- mia [J]. Am J Cancer Res，2018，8（6）：1083-1089.
[18] Melaiu O，Lucarini V，Cifaldi L，et al. Influence of the tumor microenvironment on NK cell function in solid tumors [J]. Front Immunol，2020，10：3038.
[19] 史瑞芳，姚露，贾绍昌.CAR-NK：肿瘤免疫细胞治疗新策略[J].中国肿瘤生物治疗杂志，2020，27（4）：440-444.
[20] Lu H，Zhao XY，Li ZY，et al. From CAR-T cells to CAR- NK cells：a developing immunotherapy method for hematological malignancies [J]. Front Oncol，2021，11：720501.
[21] 李欣阳.CAR-NK在肿瘤免疫治疗方面的研究进展[J].生物化工，2019，5（3）：134-136.
[22] 梁皓，肖向茜，盛望.CAR-NK细胞在癌症免疫治疗中的研究进展[J].生物技术通讯，2019，30（2）：258-263.
[23] 吕璐成，郑丽丽，赵亚娟.法匹拉韦药物全球专利布局与研发态势分析[J].科学观察，2020，15（5）：1-10.
[24] 上官晨虹，全毅恒，陈琛.基于专利计量的天麻药品研发态势分析[J].中草药，2022，53（15）：4915-4924.
[25] 吕璐成，郑丽丽，赵亚娟.克力芝药物全球专利布局与研发态势分析[J].科学观察，2020，15（5）：45-51.
[26] 蒲恒，杨兴艳.Moderna抗病毒的核酸疫苗专利分析[J].中国科技信息，2021，653（12）：19-21.
京公网安备 11010502046598号