Cytotoxicity against human peripheral blood mononuclear cells and T cell lines mediated by anti-T cell immunotoxins in the absence of added potentiator

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Abstract
Several in vitro assays have indicated that anti-T cell immunotoxins (IT), composed of monoclonal antibodies (MoAbs)conjugated to ricin A chain (RTA), are maximally effective against T cells only in the presence of potentiators. It was thought that such IT might not be sufficiently cytotoxic to deplete T cells in vivo upon administration to patients. Therefore, we have re-evaluated the in vitro assays and report herein that even with a short exposure lime (2 h), the two anti-T cell IT, H65-RTA (anti-CD5 MoAb coupled to RTA) and 4MRTA (anti-CD7 MoAb coupled to RTA30), were specifically cytotoxic for peripheral blood mononuclear cells(PBMC)in the absence of potentiators. Moreover, as has been reported for IT when tested against T cell lines, prolonging the exposure lime of the IT with PBMC from 2 h to as long as 90 h, without added potentiators, enhanced their cytotoxicity from 2- to 40-fold. In contrast, most T cell lines were more sensitive to IT in the presence of potentiator, and IT cytotoxicity was much less enhanced by prolonging the exposure time. Thus, T cell lines may not serve as accurate models to determine the efficacy of IT against PBMC in vitro or in vivo. We conclude that IT-induced cytotoxicity of PBMC can be demonstrated in vitro at pharmacologically achievable concentrations in the absence of added potentiators.