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Trispecific killer engager 161519 enhances natural killer cell function and provides anti-tumor activity against CD19-positive cancers 被引量:3
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作者 Ying Cheng Xiaodong Zheng +5 位作者 Xuefu Wang Yongyan Chen Haiming Wei Rui Sun Zhigang Tian Haoyu Sun 《Cancer Biology & Medicine》 SCIE CAS CSCD 2020年第4期1026-1038,共13页
Objective:Natural killer(NK)cells have gained considerable attention due to their potential in treating"cold tumors,"and are therefore considered as one of the new strategies for curing cancer,by using world... Objective:Natural killer(NK)cells have gained considerable attention due to their potential in treating"cold tumors,"and are therefore considered as one of the new strategies for curing cancer,by using worldwide development of their new possibilities and interventions with NK cell-related therapeutic products.Methods:We constructed a trispecific killer engager(TriKE)consisting of anti-CD16,IL-15,and anti-CD19.This TriKE was designed to attract CD19^(+)tumor cells to CD16^(+)NK cells,whereas IL-15 sustained the proliferation,development,and survival of NK cells.Results:Treatment with 161519 TriKE in the presence of CD19^(+)targets upregulated expression of CD69,CD107 a,TRAIL,IFN-γ,and TNF-α in NK cells,and significantly improved the proliferation and cytotoxicity of NK cells.NK cells"armed"with 161519 TriKE showed stronger cytolysis against CD19+targets compared with that of"unarmed"NK cells.A preclinical model of B-cell lymphoma in human peripheral blood mononuclear cell-reconstituted xenograft mice showed significant inhibition of tumor growth and prolonged overall survival after treatment with 161519 TriKE,when compared with that in control mice or mice treated with 1619 BiKE.Combined use of IL-2 was a more effective treatment with 1619 BiKE,when compared with that using 161519 TriKE.Conclusions:The newly generated 161519 TriKE enhanced the proliferation,activation,cytokine secretion,and cytotoxicity of NK cells in the presence of CD19+tumor cells.The 161519 TriKE aided inhibition of tumor growth and prolonged the overall survival of murine xenografts,and could be used to treat CD19-positive cancers. 展开更多
关键词 trispecific antibody trispecific killer engager(TriKE) NK cell B-cell lymphoma tumor immunotherapy
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NK细胞:肿瘤免疫治疗的新兴主力军 被引量:2
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作者 王立韬 白丽(指导) 《中国免疫学杂志》 CAS CSCD 北大核心 2023年第5期1059-1064,共6页
自然杀伤(NK)细胞作为人体免疫系统抵御外来病原体入侵的第一道防线,在宿主抵抗病毒感染和肿瘤的先天免疫和获得性免疫防御中发挥重要作用。近年来NK细胞以其独特优势逐渐成为肿瘤免疫治疗的新兴主力军,并在多种血液系统恶性肿瘤治疗中... 自然杀伤(NK)细胞作为人体免疫系统抵御外来病原体入侵的第一道防线,在宿主抵抗病毒感染和肿瘤的先天免疫和获得性免疫防御中发挥重要作用。近年来NK细胞以其独特优势逐渐成为肿瘤免疫治疗的新兴主力军,并在多种血液系统恶性肿瘤治疗中展现出不俗的实力。目前,针对NK细胞相关的免疫治疗手段主要包括免疫检查点抑制剂治疗、嵌合抗原受体NK治疗及双/三特异性杀伤细胞结合因子治疗等。本综述将对当前NK细胞主要的治疗手段及其在肿瘤治疗中所产生的临床效果展开叙述,以期为肿瘤患者的临床治疗提供可靠的理论依据。 展开更多
关键词 自然杀伤细胞 免疫检查点 嵌合抗原受体 双/三特异性杀伤细胞结合因子
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Antibody variable region engineering for improving cancer immunotherapy 被引量:7
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作者 Hantao Lou Xuetao Cao 《Cancer Communications》 SCIE 2022年第9期804-827,共24页
The efficacy and specificity of conventional monoclonal antibody(mAb)drugs in the clinic require further improvement.Currently,the development and application of novel antibody formats for improving cancer immunothera... The efficacy and specificity of conventional monoclonal antibody(mAb)drugs in the clinic require further improvement.Currently,the development and application of novel antibody formats for improving cancer immunotherapy have attracted much attention.Variable region-retaining antibody fragments,such as antigen-binding fragment(Fab),single-chain variable fragment(scFv),bispecific antibody,and bi/trispecific cell engagers,are engineered with humanization,multivalent antibody construction,affinity optimization and antibody masking for targeting tumor cells and killer cells to improve antibody-based therapy potency,efficacy and specificity.In this review,we summarize the application of antibody variable region engineering and discuss the future direction of antibody engineering for improving cancer therapies. 展开更多
关键词 antibody engineering bi/trispecific killer engager cancer immunotherapy chimeric antigen receptor-T(CAR-T)cell NANOBODY natural killer(NK)cell SCFV
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