Cancer immunotherapy: Co-stimulatory agonists and co-inhibitory antagonists

Department of Haematology, UCL Cancer Institute, Paul O'Gorman Building, University College London, London, UK.
Clinical & Experimental Immunology (Impact Factor: 3.04). 08/2009; 157(1):9-19. DOI: 10.1111/j.1365-2249.2009.03912.x
Source: PubMed


The generation and maintenance of immune responses are controlled by both co-stimulatory and co-inhibitory signalling through T cell co-receptors, many of which belong to the immunoglobulin-like superfamily or the tumour necrosis factor receptor superfamily. Agonistic or antagonistic monoclonal antibodies targeting these co-receptors have the potential to enhance immunity. Furthermore, their activity on the immunosuppressive regulatory T cell populations which are prevalent within many tumours provides an additional rationale for their use as anti-cancer therapies. This review summarizes the interactions between cancer and the immune system, highlighting the ways in which these new classes of immunostimulatory antibodies might enhance anti-tumour immunity and summarizing early clinical experience with their use.

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Available from: Sergio Andres Quezada
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    • "Early evidence for its potential as a target for enhancing antitumour immunity came from murine models (Leach et al, 1996), followed shortly thereafter by clinical evaluation of fully human anti-CTLA-4 antibodies. Objective responses as defined by Response Evaluation Criteria in Solid Tumours (RECIST) were documented in 10–15% of patients, though immune-related adverse events (IRAEs) involving a variety of tissues, including the gastrointestinal tract, were documented in 25–30% of cases treated at the higher doses (reviewed in Peggs et al, 2009a), highlighting the relatively narrow therapeutic index. Clinical responses appeared to correlate with the development of IRAEs, though this correlation was not absolute in either direction (Downey et al, 2007). "
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