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.

 

SynAbs & RD-Biotech have used their unique know-how to develop rat monoclonal antibodies anti mouse IL-34. This approach was really tricky as the sequence homology between IL-34 mouse and the one of the rat is more than 96 % !


Achievements

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 evaluation in humans !

Acknowledgment

" For a new therapeutic, we were looking for a one-stop-shop solution offering the entire set of tools from preclinical to clinical development. Thanks to synergetic effect, the couple RD Biotech – SynAbs has been able to first generate a mAb mouse with strong inihibitory effect, then a rat monoclonal antibody against mouse-IL34 showing the same potency effect.  The latter has been succesfully chimerized by RD Biotech to be used in prolonged in-vivo studies in mice, and the former has been humanized by this same team for human clinical trials!"

 

Dominique Heymann,

Professor of Bone Oncology,

University of Sheffield

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Anti-IL34 generation
From preclinical to clinical development: one-stop-shop mAb solution
Interleukin IL34 Case study .pdf
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