抗ROR1肿瘤抗原人源重组抗体的研发
Development of Human Recombinant Antibodies Against ROR1 Tumor Antigen.
作者信息
Bemani Peyman, Moazen Setareh, Nadimi Elham, Nejatollahi Foroogh
机构信息
Recombinant antibody laboratory, Department of Immunology, Shiraz University of Medical Sciences, Shiraz Iran.
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver BC, Canada.
出版信息
Rep Biochem Mol Biol. 2022 Jul;11(2):282-288. doi: 10.52547/rbmb.11.2.282.
BACKGROUND
Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncofetal antigen expressed on many types of cancer cells, but not normal adult cells. ROR1 antigen contributes to cancer development and progression by several signaling pathways. ROR1 expression has been associated with tumor growth, survival, and metastasis. In this study specific human recombinant antibodies were selected against ROR1 antigen for their use in cancer immunotherapy.
METHODS
Phage display technology was used to produce phage antibody from a human scFv library. Phage concentration was determined to confirm the phage rescue process. Panning procedure was performed to isolate specific scFv clones against ROR1 epitope. Phage ELISA was done to evaluate the reactivity of the selected scFvs.
RESULTS
Two specific human scFvs with frequencies of 20% and 25% were selected against ROR1 peptide. The antibodies showed specific reaction to the corresponding epitopes in phage ELISA.
DISCUSSION
Cancer targeted therapy using human specific antibodies is a new strategy, which is used in cancer therapy. The selected specific scFvs that target ROR1 epitope are human antibodies that originated from a human library and have the potential to be used in clinic in cancer immunotherapy of ROR1 positive tumors without induction of human anti mouse antibody (HAMA) response.
背景
受体酪氨酸激酶样孤儿受体1（ROR1）是一种癌胚抗原，在多种癌细胞上表达，但不在正常成人细胞上表达。ROR1抗原通过多种信号通路促进癌症的发生和发展。ROR1的表达与肿瘤生长、存活和转移有关。在本研究中，筛选了针对ROR1抗原的特异性人重组抗体，用于癌症免疫治疗。
方法
利用噬菌体展示技术从人单链抗体库中制备噬菌体抗体。测定噬菌体浓度以确认噬菌体拯救过程。进行淘选程序以分离针对ROR1表位的特异性单链抗体克隆。采用噬菌体酶联免疫吸附测定法评估所选单链抗体的反应性。
结果
筛选出两种针对ROR1肽的特异性人单链抗体，频率分别为20%和25%。这些抗体在噬菌体酶联免疫吸附测定法中对相应表位显示出特异性反应。
讨论
使用人特异性抗体的癌症靶向治疗是一种用于癌症治疗的新策略。所选的针对ROR1表位的特异性单链抗体是源自人抗体库的人抗体，有潜力用于ROR1阳性肿瘤的癌症免疫治疗临床应用，而不会诱导人抗鼠抗体（HAMA）反应。
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