Bispecific antibodies which are able to bind simultaneously with two different targets have various advantages such as overcoming resistance of single drug, increasing efficacy and reducing production expense. Therefore, many multinational biotech firm/pharmaceuticals have been trying to develop various formats for generation of bi/multi-specific antibodies. Heterodimeric Fc is one of the attractive platform technology that facilitate construction of bispecific antibodies with IgG-like format as well as Fc-fusion proteins.

We have developed high yield heterodimeric Fc technology by engineering CH3 interface of IgG. Heterodimeric Fc not only retain natural Fc properties, including physicochemical stability, long serum half-life, and immune system recruiting ability but also minimize potential immunogenicity caused by artificial mutation. Heterodimer Fc technology can be applied for generation of potent therapeutic antibodies and proteins.

Cytokines represent a large family of secreted proteins that act in both an autocrine and paracrine manner to regulate a myriad of cellular responses that influence both innate and adaptive immunity. Tumor-targeting antibody (Ab)-fused cytokines, referred to as immunocytokines, are designed to increase antitumor efficacy and reduce toxicity through the tumor-directed delivery of cytokines. Immunocytokines are being explored for several cytokines including IFNα, IFNγ, IL-2, IL-12, IL-15 and IL-21.

We have developed heterodimeric immunoglobulin Fc-fused mouse IL12 (mIL12) in a monovalent binding format(mono-mIL12-Fc) to generate long-acting mIL12 in the naturally occurring heterodimeric form. Heterodimeric-Fc-fused IL12 is a suitable format for augmenting adaptive CD8+ T cell immune responses, providing a practical alternative to the systemic administration of IL12 for anti-tumor therapy.

We can apply this Fc-fusion cytokine / immunocytokine technology to other cytokines and diverse antigens, consequently a purpose of our further study is to make potential and powerful cancer therapy drug.