The Effect of recombinant chimeric mAb14 on the growth of humanized CDX engrafted mice

Natural killer (NK) cells belongs to the innate immune system that has an essential role in attacking rapid tumor species and inhibiting their growth. These cells can be effected by set of activator and inhibitor signals induced antigen carried by the target cells. NKp44 known as natural cytotoxicity receptor 2 (NCR2) is expressed on NK cells, which interacts with variety of antigens. Those interactions lead to the inhibition of NK cells via ITIM domain.

Proliferation cell nuclear antigen (PCNA) is a nuclear protein found in all replicating cells, associated with DNA replication and repair. Our previous studies discovered overexpression and translocation of the PCNA in tumor cells. Membrane expression of PCNA in the tumor can interact with NKp44 isoform 1 and as a result, it works as an immune checkpoint (IC). Previous In-Vivo studies revealed tumor growth inhibition mediated by mouse anti-PCNA antibody. In our work, we improved recombinant chimeric anti-PCNA antibody (rC14). We demonstrated its effect in the inhibition of humanized CDX engrafted in NSG mice. Moreover, we found that rC14 demonstrated the same level of cancer growth inhibition as in Cetuximab, which is FDA approved drug. We cherish a desire of anticipation that this new drug can also be clinically approved as a new immune checkpoint inhibitor.