Anti-IL34 mAb : from Preclinical to Clinical

Interleukin-34 is a cytokine of 213 amino-acid activating macrophages. Our partner wished to develop an anti human IL-34 and evaluate its therapeutic effect in inflammatory processes.

In this context, we've been able to develop a specific mouse monoclonal antibody to human IL- 34. Tested in vitro, some of these antibodies have shown interesting inhibitory effects, but before starting the in vivo human trials, our partner wanted to develop in vivo tests in mice.

Despite the high sequence homology that existed between the rat and mouse, 11 monoclonal antibodies anti rat anti mouse IL-34 were obtained !

These clones have been evaluated in vitro and one IgG1 kappa « LO-M IL-34 » has demonstrated inhibitory properties similar to mouse anti human IL-34. To enable its prolonged in vivo use in mice and alleviating the risk to be rapidly neutralized by anti rat mouse antibodies, the variable sequences of the LO-MIL-34 were subcloned in an expression vector comprising mouse constant regions to obtain a new version of LO-M IL34 chimerized mouse. After production in CHO cells, chimerised LO-MIL-34 was then reassessed by our client and showed inhibitory property identical to LO-MIL-34. Mouse anti human IL-34 antibody have been humanized by SYnAbs in order to start clinical evaluation.