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Reduction of EGP‐2‐positive pulmonary metastases by bispecific‐antibody‐redirected T cells in an immunocompetent rat model
Author(s) -
Kroesen B. J.,
Helfrich W.,
Bakker A.,
Wubbena A. S.,
Bakker H.,
Kal H. B.,
The T. H.,
De Leu L.
Publication year - 1995
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910610612
Subject(s) - in vivo , monoclonal antibody , transfection , t cell receptor , in vitro , t cell , cancer research , antigen , receptor , biology , antibody , immunotherapy , cell culture , microbiology and biotechnology , immune system , immunology , medicine , biochemistry , genetics
Abstract 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. © 1995 Wiley‐Liss, Inc .