HCMV37

Antibody Name: HCMV37 (IgG2a|k) (VH SGIA | VL kVI)
References: Tempest, P.R., White, P., Buttle, M., Carr, F.J. and Harris, W.J. "Identification of framework residues required to restore antigen binding during reshaping of a homoclonal antibody against the glycoprotein gB of human cytomegalovirus" Int. J. Biol. Macromol. (1995) 17:37-42.
Donor Antibody: mouse
Acceptor Antibody: Human IgG1 | k
Antigen: gB envelope glycoprotein of human cytomegalovirus (HCMV)
Laboratory: Scotgen Biopharmaceuticals, UK; University of Aberdeen, UK
Design: Chose NEWM and REI FRs because the structures are known and humanised mAbs based on them have been well-tolerated in patients.
Frameworks: VH NEWM | VL REI
CDRs: All 6 VH and VL, Kabat Definition.
Backmutations: Modifications to human FRs
VH S27Y S107T L108T
VL T39K Y71F L104V T107K
To accomodate restriction sites
VL M4L Q105V
Two versions:
SITN VH TFS28-30SIT R94N
SITTRN VH TFS28-30SIT LV70-71TR R94N
Binding: Used immunoprecipitation assays so affinity not reliably determined but thought to be comparable to mouse. Best version seems to be SITTRN although discussion focusses on SITN and 71:H thought not to be important.
Expression: Rat myeloma YB2/0
Comment: Mouse residues 28-30:H known to exacerbate an immunogenic response in humans.
Clinical Indication: Herpes (HCMV) infections in immunocompromised individuals.

explanation of symbols and abbreviations

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