Dong Bin, Zhou Changhua, He Ping, Li Jing, Chen Siqi, Miao Ji, Li Qing, Wang Zhong
a School of Pharmaceutical Sciences , Sun Yat-Sen University , Guangzhou , China.
b Centre for Cellular & Structural Biology , Sun Yat-Sen University , Guangzhou , China.
Cancer Biol Ther. 2016 Apr 2;17(4):364-70. doi: 10.1080/15384047.2016.1139266. Epub 2016 Feb 1.
One of the most active fields in cancer immunotherapy is the study of bispecific antibodies, which engage immune cells to kill cancer cells. However, a variety of issues are associated with most of current bispecific antibody formats. In this study, we present a novel bispecific antibody, BiSS (Bispecific antibody with Single domain, Single domain antibodies), which was constructed by linking 2 single domain antibodies, anti-CEA and anti-CD16, in tandem. Unlike most other bispecific antibodies, the BiSS antibody can be expressed and purified from E.coli in large quantities. By recruiting natural killer cells (NK cells) to CEA-positive cancer cells, BiSS led to cancer cell death in vitro. In xenograft models, the BiSS protein blocked cancer progression. The data suggested that the single domain-based bispecific antibody BiSS was functional and can be potentially applied to a broad range of immunotherapies.
癌症免疫疗法中最活跃的领域之一是双特异性抗体的研究,这种抗体可促使免疫细胞杀死癌细胞。然而,目前大多数双特异性抗体形式都存在各种问题。在本研究中,我们展示了一种新型双特异性抗体BiSS(具有单结构域的双特异性抗体,单结构域抗体),它是通过串联连接两种单结构域抗体——抗癌胚抗原(CEA)和抗CD16构建而成。与大多数其他双特异性抗体不同,BiSS抗体能够在大肠杆菌中大量表达和纯化。通过将自然杀伤细胞(NK细胞)募集到CEA阳性癌细胞,BiSS在体外导致癌细胞死亡。在异种移植模型中,BiSS蛋白阻止了癌症进展。数据表明,基于单结构域的双特异性抗体BiSS具有功能,并且有可能应用于广泛的免疫疗法。