REDUCTION OF EGP-2-POSITIVE PULMONARY METASTASES BY BISPECIFIC-ANTIBODY-REDIRECTED T-CELLS IN AN IMMUNOCOMPETENT RAT MODEL

Effectiveness of bispecific-monoclonal-antibody (B5MAb)-mediated cellu lar anti-tumour activity was evaluated in vitro and in vivo in relatio n to the additional need for T-cell activation in a new immunocompeten t rat tumour model. L37 tumour cells, derived from a squamous-cell car cinoma of the lung of Wag/Rij rats, were transfected with the cDNA cod ing for the human 38-kDa transmembrane pan-carcinoma-associated antige n 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 th e T-cell receptor of the rat, was made and allowed specific lysis of E GP-2-transfected L37 tumour cells by activated rat T lymphocytes in vi tro. In vivo T-cell activation, assessed by up-regulation of IL-2-rece ptor expression, could be induced by daily injection of rat rlL-2. Int ravenous treatment of tumour-bearing EGP-2-positive L37 tumour with BI S-19 together with rat rlL-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 estab lished tumours. Immune activation prior to or during treatment with Bs MAbs, as achieved with IL-2, appears to be a prerequisite for successf ul treatment. (C) 1995 Wiley-Liss, Inc.