EGFR-targeted IL-2/IL-10 dual cytokine fusion protein DK210 (EGFR)

A dual cytokine fusion protein comprised of high-affinity interleukin-10 (IL-10), fused to a single chain variable fragment (scFv) scaffolding system that is linked to wild-type interleukin-2 (IL-2) in the hinge region of the scFv, in which six complementarity determining regions (CDRs) of the scFv are replaced by CDRs from an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, with potential immunomodulating and antineoplastic activities. Upon subcutaneous administration, EGFR-targeted IL-2/IL-10 dual cytokine fusion protein DK210 (EGFR) targets and binds to EGFR expressed on tumor cells. This allows the IL-2 moiety to specifically bind to IL-2 receptor (IL-2R) and activate IL-2R-mediated signaling in CD8+ T cells in the tumor microenvironment (TME). This enhances cytotoxic T-lymphocyte (CTL)-mediated cytotoxic immune responses against tumor cells. IL-10 stimulates the differentiation and expansion of tumor specific cytotoxic CD8+ T cells, thereby further enhancing the CTL-mediated cytotoxic immune responses against tumor cells. IL-10 may also reduce the toxicities of IL-2 by suppressing the secretion of pro-inflammatory cytokines associated with IL-2 toxicities. EGFR, overexpressed by a variety of cancer cell types, plays a key role in tumor cell proliferation, tumor angiogenesis and radio- and chemoresistance.