The bispecific anti-CD3 x anti-CD155 antibody mediates T cell immunotherapy for human prostate cancer

被引:13
作者
Zhao, Huijun [1 ,2 ]
Ma, Juan [1 ,2 ]
Lei, Ting [1 ,2 ,3 ]
Ma, Wanru [2 ]
Zhang, Man [1 ,2 ,3 ]
机构
[1] Capital Med Univ, Beijing Shijitan Hosp, Dept Clin Lab, 10 Tieyi Rd, Beijing 100038, Peoples R China
[2] Beijing Key Lab Urinary Cellular Mol Diagnost, Beijing 100038, Peoples R China
[3] Peking Univ, Dept Clin Lab, Sch Clin Med 9, Beijing 100038, Peoples R China
基金
北京市自然科学基金;
关键词
Prostate cancer; Immunotherapy; CD155; Bispecific antibody; COLONY-STIMULATING FACTOR; POLIOVIRUS; RECEPTOR; TRIAL; RADIOTHERAPY; PLACEBO; CD155; PSA;
D O I
10.1007/s10637-018-0683-9
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Expression of CD155 differs between tumor and normal tissues, and high expression of this molecule can promote tumor metastasis. Here, we investigate whether CD155 can serve as a target for T cell-mediated immunotherapy of human prostate cancer. We first demonstrate that prostate cancer cells, including PC-3, PC-3 M, and LNCAP cells, express CD155 at high levels. Next, the specific cytotoxic activity of activated T cells (ATCs) armed with a novel anti-CD3 x anti-CD155 bispecific antibody (CD155Bi-Ab) against tumor cells was evaluated by flow cytometry, lactate dehydrogenase assay (LDH), and ELISA. In contrast to unarmed ATCs, an increase in the cytotoxic activity of CD155Bi-armed ATCs against tumor cells was observed at an effector/target (E/T) ratio of 5:1. Moreover, CD155Bi-armed ATCs secreted more IFN-gamma, TNF-alpha, and IL-2 and expressed higher levels of the activation marker CD69 than did unarmed ATCs. As CD155 Bi-Ab enhances the ability of ATCs to kill prostate cancer cells, CD155 is an effective target for cytotoxic T cells in human prostate cancer therapy.
引用
收藏
页码:810 / 817
页数:8
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