Antibody Name: Campath-9 (clone YNB46.1.8SG2B1.19)
References: Gorman, S.D., Clark, M.R., Routledge, E.G., Cobbold, S.P. and Waldmann, H. "Reshaping a therapeutic CD4 antibody." Proc. Natl. Acad. Sci. USA (1991) 88: 4181-4185.
Donor Antibody: rat
Acceptor Antibody: Human IgG1 | k (Campath-9H)
Antigen: human CD4
Laboratory: Pathology Dept., University of Cambridge, UK
Design: Comparison of two VH framework regions, NEWM because it worked in the past and KOL because it has better sequence identity to Campath-9.
Frameworks: VH human KOL or NEWM | VL human REI (modified as in Campath-1H.)
CDRs: All 6 from VH and VL, Kabat Definition.
Backmutations: P108T:H in KOL, but the proline was restored in another version without adverse effect. VH S27F S30T in NEWM as in Campath-1H
Binding: The avidity of the KOL-based mAb was "slightly reduced" compared to the chimaeric by immunofluorescence staining and was effective in cell-mediated lysis. 3-fold reduction in binding to CD4+ cells and retained biological activity in ADCC assays. "In contrast, the NEW-based CD4 antibody, though still retaining specificity for CD4, had a considerably reduced relative binding avidity and had no biological activity".
Expression: Dihydrofolate reductase-deficient Chinese hamster ovary cells (CHO)
Comment: First comparison of FR regions showing that the 'bestfit' strategy leads to a better reshaped mAb.
Clinical Indication: The humanised mAb allows a means of establishing a state of immunological tolerance.

explanation of symbols and abbreviations

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