Development of a mouse-feline chimeric antibody against feline tumor necrosis factor-alpha

DOKI, Tomoyoshi; TAKANO, Tomomi; HOHDATSU, Tsutomu

In humans, infliximab is used as a therapeutic drug for rheumatoid arthritis (RA). In addition to neutralizing human TNF-alpha, which is a factor aggravating the pathology of RA, infliximab directly injures TNF-alpha-producing cells expressing TNF-alpha on the cell surface through antibodydependent cellular cytotoxicity and complement-dependent cytotoxicity. Infliximab exhibits its treatment effect against RA through these actions. Infliximab is repeatedly administered at 4-or 8-week intervals until RA remission is observed. Accordingly, to reduce antigenicity for humans, infliximab is expressed in mammalian cells as a mouse-human chimeric antibody prepared by fusing the variable region of mouse mAb and the constant region of human antibody [20] . Human anti-mouse antibody response to the mouse-human chimeric mAb was reduced compared to that of the mouse mAb response, and the adverse reactions after administration were also reduced. Based on these findings, it was hypothesized that the feline anti-mouse antibody response and the development of adverse reactions after administration may be reduced by substituting the amino acid sequence of the feline antibody constant region for that of the mAb 2-4 constant region.