Medical Faculty Carl Gustav Carus, Institute of Immunology, Technical University Dresden, Dresden, Germany.
Prostate. 2011 Jun 15;71(9):998-1011. doi: 10.1002/pros.21315. Epub 2010 Dec 28.
Prostate cancer (PCa) is the most common malignant disease in men. Novel treatment options are needed for patients after development of metastatic, hormone-refractory disease or for those who have failed a local treatment. The prostate stem cell antigen (PSCA) is expressed in >80% of primary PCa samples and bone metastases. Its expression is increased both in androgen-dependent and independent prostate tumors, particularly in carcinomas of high stages and Gleason scores. Therefore, PSCA is an attractive target for immunotherapy of PCa by retargeting of T cells to tumor cells.
A series of different bispecific antibody formats for retargeting of T cells to tumor cells were described but, only very limited data obtained by side by side comparison of the different antibody formats are available. We established two novel bispecific antibodies in different formats. The functionality of both constructs was analyzed by FACS and chromium release assays. In parallel, the release of pro-inflammatory cytokines was determined by ELISA.
Irrespective of the underlying antibody format, both novel bispecific antibodies cause an efficient killing of PSCA-positive tumor cells by pre- and non-pre-activated T cells. Killing and release of pro-inflammatory cytokines requires an antigen specific cross-linkage of the T cells with the target cells.
前列腺癌（PCa）是男性最常见的恶性疾病。对于发生转移性、激素难治性疾病的患者，或对于那些局部治疗失败的患者，需要新的治疗选择。前列腺干细胞抗原（PSCA）在>80%的原发性 PCa 样本和骨转移中表达。其表达在雄激素依赖性和非依赖性前列腺肿瘤中均增加，特别是在高分期和高 Gleason 评分的癌中。因此，PSCA 是通过将 T 细胞重定向到肿瘤细胞来进行 PCa 免疫治疗的有吸引力的靶标。
描述了一系列用于将 T 细胞重定向到肿瘤细胞的双特异性抗体格式，但仅通过并排比较不同抗体格式获得了非常有限的数据。我们建立了两种不同格式的新型双特异性抗体。通过 FACS 和铬释放测定分析了两种构建体的功能。同时，通过 ELISA 测定了促炎细胞因子的释放。
无论基础抗体格式如何，两种新型双特异性抗体均可通过预激活和非预激活的 T 细胞有效杀伤 PSCA 阳性肿瘤细胞。杀伤和释放促炎细胞因子需要 T 细胞与靶细胞的抗原特异性交联。
