靶向CD20和HLA-DR的双特异抗体在非霍奇金淋巴瘤中的抗肿瘤研究

Despite the unprecedented success of rituximab in treating NHL, a subgroup of patients do not respond. HLA-DR antigen is an attractive target for antibody-based lymphoma therapy because HLA-DR is highly expressed on a range of hematologic malignancies, and it is closely related to CD20, furthermore, HLA-DR mAb can directly induce cytotoxicity in addition to mediating ADCC and CDC. We have developed CD20-HLA-DR DVD-Ig for targeting both CD20 and HLA-DR with an biocharacteristics similar to that of its parental antibodies, exhibited more highly specific anti-tumor activities. We will investigate the mechanism bispecific antibody of a specific anti-CD20/HLA-DR bispecific antibody against NHL in vitro and in in vivo. It may be a promising therapeutic agent for the treatment of NHL which are refractory to conventional chemotherapy and immunotherapy.

尽管抗CD20单克隆抗体rituximab治疗NHL已取得了革命性的胜利，但仍有部分患者对rituximab治疗不敏感。HLA-DR在多种造血系统恶性肿瘤中高表达，和CD20关系密切，而HLA-DR单克隆抗体除了介导ADCC和CDC外还可以导致细胞毒性杀伤作用，引起了人们探索用抗HLA-DR单克隆抗体靶向治疗淋巴瘤的兴趣。我们前期构建了靶向CD20和HLA-DR的新型双特异抗体CD20-HLA-DR DVD-Ig ，它很好地继承了各亲本抗体的生物学特征，表现出更强的抗肿瘤特性。本项目中，我们将通过体内外实验探讨该双特异性抗体在NHL中的抗肿瘤作用并阐明其机理，为常规化疗和免疫治疗不敏感的NHL提供有效的靶向抗体制剂。