How Caerus utilized a non-conventional development strategy for an anti-human fractalkine receptor antibody

The directive:

Caerus was tasked with the development of antibodies specific to human CX3CR1 (a.k.a., fractalkine receptor) as a therapeutic for inflammatory diseases.

 

The problem:

CX3CR1, also known as fractalkine receptor, is a 7-transmembrane GPCR protein. CX3CR1 is also a highly conserved protein, with 67% identity between mouse and human sequences. This hydrophobic protein is highly conserved in the extracellular domains to its mouse homolog, rendering conventional immunization approaches ineffective.

 

The solution:

Multiple subtractive immunization strategies were performed using cells that did not express antigen to subtract and cells that expressed antigen for immunization. To overcome these impediments, the expert team at Caerus used a mouse strain predisposed to autoimmunity, effectively reducing the barrier to breaking tolerance for this conserved antigen

 

The result:

This expertise allowed Caerus to rapidly generate several high-affinity antibodies for the client, overcoming the barrier to this technically challenging receptor (GPCR, human CX3CR1), and allowing them to generate novel IP and advance the development of their therapeutic.