Increased therapeutic effect of vinca alkaloids targeted to tumour by a hybrid-hybrid monoclonal antibody

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

“…We have discussed previously the in vivo inhibition of tumour growth by targeting unmodified vinblastine to tumour masses by virtue of the bispecificity of the hybridhybrid antibody 28-19-8 [4,[6][7][8]. Using the same xenograft model we report here the results obtained when initiation of treatment is withheld until the tumours are growing in exponential phase with each mouse carrying approximately 2% of its body weight as tumour.…”

“…In earlier reports we have demonstrated that when vinblastine is targeted to tumours by the hybrid-hybrid 28-19-8, at least ten times as much vinblastine is located on the tumour than can be located using vinblastine alone [6,8]. This ability of the bispecific antibody to concentrate unmodified drug on tumour masses resulted in significant suppression of tumour growth when treatment with hybrid-hybrid and vinblastine commenced 9-11 days after tumour implantation [7,8]. Our results in this report show that similar suppression of tumour growth was obtained when the initiation of treatment was delayed until day 23, by which time the tumours were in exponential phase, doubling in volume every 5 days.…”

“…The general morphology of tumours was assessed on sections stained with haematoxylin and eosin and the presence of acid proteoglycans was demonstrated with 1% Alcian blue at pH 3.0. Immunocytochemistry was performed on the dewaxed and hydrated 4 btm sections by a modification of the previously described method [7]. Briefly, CEA was detected with 11.285.14 [5,20,22] the parental anti-CEA antibody used in the fusion producing the hybrid-hybrid 28-19-8.…”

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).…”

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

“…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).…”