DAVID J. FLAVELL:  THURSDAY 30 MARCH 2006, 19:05

Strategies to improve the efficacy of immunotoxin therapies

David J. Flavell
University of Southampton, The Simon Flavell Leukaemia Research Lab, Cancer Sciences, Southampton, UK

Immunotoxins have proven potent anti-tumour effects in cancer patients but their clinical use can be severly restricted by a variety of dose-limiting toxicities. A major goal should therefore be to find ways of increasing the potency of this class of immunotherapeutic without increasing their toxicity. There are several ways in which this might be achieved ranging from improving the internalization and routing of immunotoxin in the target cell to induction of complementary pro-apoptotic pathways that act synergistically with toxin action. We will present three separate lines of experimental evidence demonstrating ways in which immunotoxin therapeutic potency directed against human B- and T-lineage leukaemias and lymphomas can be improved upon namely through (a) the utility of cocktails of immunotoxins recognising different target molecules (b) the harnessing of host antibody dependent cellular cytotoxicity (ADCC) and (c) the utility of antibodies that deliver pro-apoptotic signals to the target tumour cell. The potential for clinical utility of these three different approaches will be discussed and the means for practical application considered.

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