Local secretion of a chimeric anti-CD4 antibody protects against graft rejection in the NOD mouse

Background. Engineering a graft to secrete its own immunosuppressive antibo dies may minimize the risks associated with current high dose systemic immu nosuppression. Methods and Results. A beta cell insulinoma cell line (NIT-1) was transfect ed with genes encoding a chimeric anti-CD4 antibody. The NIT-1 cells secret ed functional chimeric anti-CD4 antibody that bound to the CD4 molecule on mouse thymocytes and inhibited in vitro proliferation of CD4(+ve) T cells. Both test and control transfected cell. lines grew at a similar rate in imm unodeficient mice. In immunocompetent NOD mice, NIT-1 cells are normally re jected by a cellular immune response against the SV40 T antigen. Although c ontrol transfected NIT-1 cells were rapidly rejected by NOD mice, anti-CD4 secreting NIT-1 cells grew significantly better and were able to form tumor s at the site of injection. Conclusions. The local secretion of chimeric anti-CD4 antibody from transfe cted cells can contribute to graft survival in our transplantation model.