双特异性单克隆抗体和人T细胞对异种移植的人类肿瘤的治疗作用

Cure of xenografted human tumors by bispecific monoclonal antibodies and human T cells.

作者信息

Renner C, Jung W, Sahin U, Denfeld R, Pohl C, Trümper L, Hartmann F, Diehl V, van Lier R, Pfreundschuh M

机构信息

Medizinische Klinik und Poliklinik, Universität des Saarlandes, Homburg, Germany.

出版信息

Science. 1994 May 6;264(5160):833-5. doi: 10.1126/science.8171337.

DOI:10.1126/science.8171337

PMID:8171337

Abstract

Tumor immunotherapy should increase both the number of T cells that kill the tumor and the likelihood that those cells are activated at the tumor site. Bispecific monoclonal antibodies (Bi-mAbs) were designed that bound to a Hodgkin's tumor-associated antigen (CD30) on the tumor and to either CD3 or CD28 on the T cell. Immunodeficient mice were cured of established human tumors when mice were treated with both the CD3-CD30 and the CD28-CD30 Bi-mAbs and then given human peripheral blood lymphocytes that had been incubated with the CD3-CD30 Bi-mAb and cells that expressed CD30. The enrichment of human T cells within the tumor and the fact that established tumors can be cured may indicate in situ activation of both the T cell receptor and the costimulatory pathway.

摘要

肿瘤免疫疗法应增加杀伤肿瘤的T细胞数量以及这些细胞在肿瘤部位被激活的可能性。设计了双特异性单克隆抗体（双特异性抗体），使其与肿瘤上的霍奇金肿瘤相关抗原（CD30）以及T细胞上的CD3或CD28结合。当用CD3 - CD30和CD28 - CD30双特异性抗体治疗小鼠，然后给予已与CD3 - CD30双特异性抗体孵育的人外周血淋巴细胞和表达CD30的细胞时，免疫缺陷小鼠体内已形成的人类肿瘤被治愈。肿瘤内人类T细胞的富集以及已形成的肿瘤能够被治愈这一事实，可能表明T细胞受体和共刺激途径均发生了原位激活。