YTH12.5

Antibody Name: YTH12.5.14.2 (IgG2b)
References: Routledge, E.G., Lloyd, I., Gorman, S.D., Clark, M. and Waldmann, H. "A humanized monovalent CD3 antibodywhich can activate homologous complement." Eur. J. Immunol. (1991) 21:2717-2725.
Donor Antibody: rat
Acceptor Antibody: Human IgG1 (allotype G1m) | λ Made bivalent and monovalent (1Fab, 1FC) mAbs.
Antigen: CD3 antigen complex on human T cells
Laboratory: Cambridge University, UK
Design: Chose most similar human FR V regions.
Frameworks: VH VH26-D-J (Humighat)(SGIII) | VL SUT (λSGVI)
CDRs: All 6 from VH and VL, Kabat Definition.
Backmutations: None
Binding: Bivalent humanised mAb bound to HPB-ALL cells 1.3-fold less than rat in competition binding assays.
Monovalent had 6-fold lower avidity but was better in complement-mediated cell lysis assays.
Expression: DHFR- Chinese Hamster Ovary cells
Comment: First humanization of a Vλ region. Monovalent form less likely to modulate the CD3 antigen.
Clinical Indication: For organ rejection, autoimmunity (immunosuppressive) and T-cell lymphoma.

explanation of symbols and abbreviations

José Saldanha © 1997-8. Birkbeck College, London WC1E 7HX.