Screening and antitumor effect of an anti-CTLA-4 nanobody
Screening and antitumor effect of an anti-CTLA-4 nanobody
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DOI：
10.3892/or.2017.6131
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发表时间：
2018
期刊：
影响因子：
4.2
通讯作者：
XIAOLING LU
中科院分区：
文献类型：
--
作者：
RUIRONG WAN;AIQUN LIU;XIAOQIONG HOU;ZONGQIANG LAI;JIEPING LI;NUO YANG;JUNTAO TAN;FENGZHEN MO;ZIXI HU;XIAOMEI YANG;YONGXIANG ZHAO;XIAOLING LU
Abstract. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a critical negative regulator of immune responses. CTLA-4 is rapidly upregulated following T-cell activation, and then binds to B7 molecules with a higher af nity than CD28. CTLA‐4 may abolish the initiation of the responses of T cells by raising the threshold of signals required for full activation of T cells, and it also may terminate ongoing T-cell responses. This regu- latory role has led to the development of monoclonal antibodies (mAbs) designed to block CTLA-4 activity for enhancing immune responses against cancer. mAbs have several disad- vantages including high production cost and unstable behavior. Nanobodies (Nbs) are single-domain antigen-binding frag- ments derived from the camelid heavy-chain antibodies, which are highly attractive in cancer immunotherapy due to their small size, high speci city, and stability. We selected CTLA‐4‐speci c Nbs from a high quality dromedary camel immune library by phage display technology. Four positive colonies were sequenced and classi ed based on the amino acids sequences in the CDR3 region. These Nbs recognized unique epitopes on CTLA-4 and displayed high binding rates when used on PHA-stimulated human T cells. Treatment of B16 melanoma-bearing C57BL/6 mice with anti-CTLA-4 nanobody 16 (Nb16) delayed melanoma growth and prolonged the survival time of mice. These data indicate that anti-CTLA-4 Nbs selected from a high quality phage display library may be effective for the treatment of patients with tumors.
