Scandinavian Journal of Immunology · 1996 · 16 citations · 0 references
PharmacyBiotechnologyImmunologyAntibody EngineeringClinical ImmunologyMolecular ImmunologyAntibody CharacterizationAntibody Fragment EngineeringAntibody Specificity EngineeringAntibody StructureChimeric AntibodiesTherapeutic Antibody DevelopmentAntibody Structure-function RelationshipsCell Proliferation StimulationChimeric Antibody ProductionCytokine Mediator ReleaseCytokine Release AssaysHuman Anti-mouse Antibody ResponseImmunosuppressive Function
Murine anti-CD3 monoclonal antibodies (MoAbs) are used in clinical practice for immunosuppression. However, there are two major drawbacks to this treatment: the associated cytokine release syndrome and human anti-mouse antibody response. To overcome these side-effects, the authors generated a chimeric anti-human CD3 single chain antibody, scUCHT1. It is an IgM variant of UCHT1, a mouse IgG1 MoAb directed against human CD3. scUCHT1 consists of the light and heavy variable chain binding domains of UCHT1 and a human IgM Fc region (CH2 to CH4). scUCHT1 was produced by COS-7 and SP2/0 transfectants, and mainly assembled in a dimeric form. It retained the binding specificity and affinity of the parental MoAb UCHT1. In contrast to UCHT1, scUCHT1 did not induce T-cell proliferation and cytokine release (TNF-alpha and IFN-gamma) in in vitro assays. These results suggest that the engineered chimeric anti-CD3 single chain antibody (scUCHT1) may be useful in clinical immunosuppressive treatment.