Cytokines are regulatory proteins that can stimulate or inhibit components of the immune system. Indeed, cytokines can be used in vivo to promote or block inflammatory processes and immune reactions to serious conditions, such as cancer and certain infectious diseases. Some recombinant cytokines, growth factors and immunomodulatory proteins have gained marketing approval and are commonly used in the clinic (e.g., interleukin-2, TNF, GM-CSF, G-CSF, interferon-a, interferon-b, interferon-g). However, cytokines are often toxic at low doses (i.e., few milligrams per patient), which may limit escalation to therapeutically active regiments. As therapeutic cytokines usually do not preferentially localize at sites of disease, there is a clear pharmaceutical opportunity in linking them to antibodies for delivery to diseased tissue, thus improving potency and reducing side effects.

Over the years, the Philogen group has developed and extensively validates human monoclonal antibodies capable of selective localization at sites of disease (e.g., L19, F8, F16) (Neri et al. 1997; Tarli et al. 1999; Brack et al. 2006; Villa et al. 2008). Philochem scientists have developed four immunocytokines based on IL2, TNF and IL10, which are currently being investigated in clinical trials in patients with cancer or with rheumatoid arthritis (L19-IL2, F16-IL2, L19-TNF, F8-IL10). Furthermore, we have systematically explored and tested in animal models of disease (in collaboration with the group of Prof. Dario Neri at ETH Zürich) fusion proteins of Philochem’s antibodies with cytokines, interferon and growth factors.