AT13/5

Antibody Name: AT13/5
References: Ellis, J.H., Barber, K.A., Tutt, A., Hale, C., Lewis, A.P., Glennie, M.J., Stevenson, G.T. and Crowe, J.S. "Engineered anti-CD38 monoclonal antibodies for immunotherapy of multiple myeloma" J. Immunol. (1995) 155:925-937.
Donor Antibody: mouse
Acceptor Antibody: Human IgG1 | k
Chimaeric (Mouse/Human) FabFc2
Antigen: CD38, surface antigen on myeloma cells
Laboratory: Wellcome Foundation, UK; Tenovus Research, UK
Design: Modelled mouse and humanised Fv regions with AbM. Chose FR mutations based on previous humanisations and then analysed models to select four further areas in the heavy chain: 66-73, 28-29, 76, 78.
Frameworks: VH NEWM | VL REI (as in Campath-1H).
CDRs: All 6 VH and VL, Kabat Definition.
Backmutations: VH S27F TF28-29SL S30T VTMLVDT67-73LNITKDN F78V R94K
VL Y49S
Binding: Best binder version H3S, humanised and FabFC2 constructs showed similar high-affinity CD38 binding.
Expression: stable expession in NS0 and CHO cells
Comment: Interaction between 29:H and 78:H not modelled correctly by AbM. See also JES1-39D10. Data didn't support favouring FabFc2 construct over the humanised mAb.
Clinical Indication: Multiple myeloma

explanation of symbols and abbreviations

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