Cytokines are immunoregulatory proteins that can stimulate or inhibit cellular 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., IL2, TNF, GM-CSF, G-CSF, interferon-α, interferon-β, interferon-γ). However, cytokines are often toxic at low doses, which may limit escalation to therapeutically active regimens. 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.
Our scientists have developed immunocytokines based on IL2, IL12, TNF, IL4 and IL10, which are currently being investigated in pre-clinical and clinical studies. Furthermore, we have systematically explored and tested in models of disease (in collaboration with the group of Prof. Dario Neri at ETH Zürich) fusion proteins of Philogen’s antibodies with a diverse array of other cytokines, growth factors and other immunomodulatory compounds.
|Bootz and Neri (2016) Drug Discov. Today 21:180-9.
Neri & Sondel (2016) Curr. Opin. Immunol. 40:96-102;
Kiefer & Neri (2016) Immunol. Rev. 270:178-92;
Zegers et al. (2015) Clin. Cancer Res. 21:1151-60;
Hemmerle and Neri (2014) Int. J. Cancer, 134:467-77;
Hemmerle et al. (2014) Proc. Natl. Acad. Sci. USA. 111:12008-12
Schwager et al. (2013) J. Invest. Dematol. 133:751-8;
Gutbrodt et al. (2013) Sci. Transl. Med. 5:201ra118;
Moschetta et al. (2012) Cancer Res. 72:1814-24;
|Pasche et al. (2012) Clin. Cancer Res., 18:4092-103;
Pasche & Neri (2012) Drug Discovery Today 17:583-90;
Neri & Supuran (2011) Nature Rev. Drug Discov. 10: 767-77;
Schliemann et al. (2009) Blood 113:2275-83;
Marlind et al. (2008) Clin. Cancer Res., 14:6515-24;
Neri & Bicknell (2005) Nature Rev. Cancer 5:436-46;
Halin et al. (2003) Cancer Res. 63:3202-10;
Halin et al. (2002) Nature Biotechnol. 20:264-9;
Borsi et al. (2002) Int. J. Cancer: 102:75–85;