Suppression of well-established tumour xenografts by a hybrid-hybrid monoclonal antibody and vinblastine

Abstract

The hybrid-hybrid monoclonal antibody 28-19-8 has specificity for the tumour-associated antigen carcinoembryonic antigen and the vinca alkaloids. This bifunctional antibody has been used to target unmodified vinblastine sulphate to well-established MAWI human tumour xenografts implanted in nude mice. The highly significant suppression of tumour growth achieved throughout treatment has also been sustained for over 2 months after the withdrawal of treatment. Histological examination of excised tumours from treated animals has shown profound changes in their morphology when compared with tumours from control animals. Cells in tumours that had started to grow again after withdrawal of therapy were shown still to express carcinoembryonic antigen, the target antigen recognised by the bispecific antibody.

Generation of bispecific monoclonal antibodies for two phase radioimmunotherapy

“…From these MAbs those which could be inhibited in their binding to the immunogen by free DTPA-Y or related compounds were selected (Table I) Bispecific MAb could be purified from the quadroma supernatant using double anti-idiotype chromatography. The immunoreactivity of this bispecific anti-GIT mucin x anti-DTPA-Y-90 MAb was greater than 95% for each individual arm and is exceptionally high when compared to bispecific MAbs purified by other methods Smith et al, 1990;Lenz & Weidle, 1990).…”

Xenogeneic monoclonal antibodies in the management of cancer: control of their in vivo immunogenicity and induction of specific unresponsiveness using an antibody-drug immunoconjugate

“…We designed our experiments to be as close to the clinical situation as possible. The bispecific antibody used as antigen is an anti-tumour monoclonal antibody, which has been used to target vinblastine to established tumours (Corval'an et al, 1987b;Smith et al, 1990). It was administered to rabbits at a concentration equivalent to that desired in clinical therapy, and at this dose in the absence of VLB it was very immunogenic.…”

“…As a consequence, the amount of the therapeutic antibody that could reach the tumour is very low, and continuously decreases upon (Corvalan & Smith, 1987). This antibody has been used successfully to target free, unmodified Vinca alkaloids to tumours expressing CEA, with significant suppression of tumour growth (Corvalan et al, 1987a,b;Corvalan et al, 1988;Smith et al, 1990). In this study we 11.285.14), and spleen cells from a mouse previously immunised with vindesine-bovine serum albumin (VDS-BSA).…”

“…This hybrid-hybrid (HH) antibody designated as 28.19.8) has the capacity of binding CEA with one binding site and Vinca alkaloids with the other, the latter with an affinity constant of -5 x 108 M-1 (unpublished data) as determined by equilibrium dialysis. It has been shown, that when 'loaded' with vindesine (Corvalan et al, 1987a) or vinblastine (Corvalan et al, 1987b), it is toxic to CEA expressing cells, not only in vitro but also in vivo against human tumour xenografts in nude mice (Corvalan et al, 1988;Smith et al, 1990).…”

Immunoglobulins Secreted by a Hybrid-Hybridoma: Analysis of Chain Assemblies

“…Since the first reports of hybrid-hybridomas producing bifunctional antibodies (1,2), increased attention has been focused on their use in research and diagnostics (3,4) and in therapy (5,6,7). These hybrid-hybridomas, with antibody genes inherited from both fusion partners, secrete not only the bispecific antibody but also antibodies with the monospecific binding capabilities of both fusion parents (8,9).…”