A current focus of cancer research is the development of immunostimulatory therapeutic antibodies, based on the notion that increasing the number or activity of cytotoxic T lymphocytes, and in particular those directed against tumour-associated antigens, may achieve effective immune mediated tumour rejection. Unlike other techniques, such as the use of antibodies specific to tumour cells themselves, this approach does not rely on antigen-specificity, and accordingly is subject to risks of autoimmunity as a consequence of nonspecific activation of T cells [1]. The risks associated with such an approach have been placed firmly in the spotlight following the recent highly publicised suspension of Phase-I clinical testing of TGN1412 (see [2] for TGN1412 Investigator’s Brochure). This monoclonal antibody, one of a class of ‘superagonists’ for the immune co-stimulatory receptor CD28, was developed by TeGenero Immune Therapeutics (Würzburg, Germany) for the treatment of both autoimmune diseases [3] and leukaemia [4, 5]. Use of such antibodies for treatment of both autoimmunity and malignancy seeks to exploit the opposing functions of the antibody; in the former, the aim is the expansion of regulatory T cells for the suppression of self-directed immune responses, whereas in the latter, the aim is expansion and activation of cytotoxic T cells directed against tumour antigens. Shortly after being injected with the TGN1412, all six healthy volunteers were admitted into intensive care with rapid onset grade-IV toxicity, suffering from multi-organ failure, caused by cytokine release syndrome [6].