POTENTIAL THERAPEUTIC USE OF ANTIBODIES DIRECTED TOWARDS HUIFN-GAMMA

IFN-gamma is an important regulator of immune responses and inflammati on. Studies in animal models of inflammation, autoimmunity, cancer, tr ansplant rejection and delayed-type hypersensitivity have indicated th at administration of antibodies against IFN-gamma can prevent the occu rrence of diseases or alleviate disease manifestations. Therefore, it is speculated that such antibodies may have therapeutical efficacy in human diseases. Since animal-derived antibodies are immunogenic in pat ients several strategies are being developed in order to reduce or abo lish this human anti-mouse antibody (HAMA) response. In our laboratory , we have constructed a single-chain variable fragment (scFv) derived from a mouse antibody with neutralizing potential for human IFN-gamma. A scFv consists of only variable domains tethered together by a flexi ble linker. The scFv was demonstrated to neutralize the antiviral acti vity of HuIFN-gamma in vitro and therefore might be considered as a ca ndidate for human therapy.