Kroesen B J, Helfrich W, Bakker A, Wubbena A S, Bakker H, Kal H B, The T H, de Leij L
Department of Clinical Immunology, University Hospital Groningen, The Netherlands.
Int J Cancer. 1995 Jun 9;61(6):812-8. doi: 10.1002/ijc.2910610612.
Effectiveness of bispecific-monoclonal-antibody (BsMAb)-mediated cellular anti-tumour activity was evaluated in vitro and in vivo in relation to the additional need for T-cell activation in a new immunocompetent rat tumour model. L37 tumour cells, derived from a squamous-cell carcinoma of the lung of Wag/Rij rats, were transfected with the cDNA coding for the human 38-kDa transmembrane pan-carcinoma-associated antigen EGP-2. Intravenous inoculation of EGP-2-positive L37 cells resulted in a rapid outgrowth of EGP-2-positive tumour nodules in the lungs. A BsMAb BIS-19, recognizing EGP-2 on the transfected tumour cells and the T-cell receptor of the rat, was made and allowed specific lysis of EGP-2-transfected L37 tumour cells by activated rat T lymphocytes in vitro. In vivo T-cell activation, assessed by up-regulation of IL-2-receptor expression, could be induced by daily injection of rat rIL-2. Intravenous treatment of tumour-bearing EGP-2-positive L37 tumour with BIS-19 together with rat rIL-2 resulted in almost complete disappearance of established tumour. In contrast, animals treated with BIS-19 alone, IL-2 alone or a combination of anti-EGP-2, anti-TcR and IL-2 showed much less or no tumour reduction. These results show effectiveness of systemic treatment with BsMAbs to induce anti-tumour activity in established tumours. Immune activation prior to or during treatment with BsMAbs, as achieved with IL-2, appears to be a prerequisite for successful treatment.
在一种新的具有免疫活性的大鼠肿瘤模型中，针对T细胞激活的额外需求，对双特异性单克隆抗体（BsMAb）介导的细胞抗肿瘤活性的有效性进行了体内和体外评估。从Wag/Rij大鼠的肺鳞状细胞癌中分离出L37肿瘤细胞，用编码人38 kDa跨膜泛癌相关抗原EGP-2的cDNA进行转染。静脉注射EGP-2阳性的L37细胞导致肺部EGP-2阳性肿瘤结节迅速生长。制备了一种双特异性单克隆抗体BIS-19，它能识别转染肿瘤细胞上的EGP-2和大鼠的T细胞受体，并能在体外使活化的大鼠T淋巴细胞对EGP-2转染的L37肿瘤细胞进行特异性裂解。通过IL-2受体表达上调评估的体内T细胞激活可通过每日注射大鼠rIL-2诱导。用BIS-19联合大鼠rIL-2对携带EGP-2阳性L37肿瘤的动物进行静脉治疗，导致已形成的肿瘤几乎完全消失。相比之下，单独用BIS-19、单独用IL-2或抗EGP-2、抗TcR和IL-2联合治疗的动物肿瘤缩小很少或没有缩小。这些结果表明，用BsMAb进行全身治疗在已形成的肿瘤中诱导抗肿瘤活性是有效的。在用BsMAb治疗之前或期间进行免疫激活，如用IL-2所实现的，似乎是成功治疗的先决条件。
