0.5B

Antibody Name: 0.5B
References: Maeda, H., Matsushita, S., Eda, Y., Kimachi, K., Tokiyoshi, S. and Bendig, M. "Construction of reshaped human antibodies with HIV-neutralising activity" Hum. Antibod. Hybridomas. (1991) 2:124-134.
Donor Antibody: mouse
Acceptor Antibody: Human IgG1 | k
Antigen: V3 loop of gp120 of Human Immunodeficiency Virus (HIV) IIIB
Laboratory: Chemo-Sero-Therapeutic Research Inst., Japan; MRC Collaborative Centre, UK
Design: Tried two different FRs. Retained canonical residues. No structural modelling, but made 6 versions of the heavy chain, 1 of the light. 3 versions with NEWM FR, 3 with SGI consensus.
Frameworks: VH human NEWM (modified as in D1.3.)
VH human SGI (consensus sequence from Kabat Ed. IV 1987)
VL human REI (modified as in Campath-1H)
CDRs: All 6 VH and VL, Kabat Definition.
Backmutations: VH S30T L71V S94I (canonical residues)
VH V37M R38K A40N V48I RVTM66-69KAKL (atypical residues)
(The text says that residue 49 was changed, but this is invariant)
Binding: The NEW-based mAbs showed no detectable binding
The SGI-based mAbs all showed binding
The best version RHE | RL gave 2-fold lower affinity in comparison to mouse and chimaeric mAbs in competition binding assays to BH10 (a synthetic 20-aa peptide basd on the sequence of the RP135 region of gp120 from HIV-IIIB). There was also a 2-fold reduction in virus-neutralisation.
Expression: transient expression in cos cells
Comment: "This suggests that selecting a set of human FRs that show a high degree of homology to the FRs in the rodent antibody is an important step in insuring the design of successful reshaped human antibodies."
Clinical Indication: Prevention and treatment of HIV infections, but since the mAb is type-specific it will be limited to certain patients.

explanation of symbols and abbreviations

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