Immunocytokines (ICs) are a class of molecules created by linking
tumor-reactive
monoclonal antibodies to
cytokines that are able to activate immune cells.
Tumor selective localization is provided by the ability of the mAb component to bind to molecules found on the
tumor cell surface or molecules found selectively in the
tumor microenvronment. In this way the
cytokine component of the immunocytokine is selectively localized to sites of
tumor and can activate immune cells with appropriate receptors for the
cytokine. Immunocytokines have been made and tested by us, and others, using a variety of
tumor-reactive mAbs linked to distinct
cytokines. To date, the majority of clinical progress has been made with ICs that have linked human
interleukin-2 (
IL2) to a select number of
tumor reactive mAbs that had already been in prior clinical testing as non-modified mAbs (Figure 1). Here we briefly review the background for the creation of ICs, summarize current clinical progress, emphasize mechanisms of action for ICs that are distinct from those of their constituent components, and present some directions for future development and testing.