| Abstract: |
L and H chain cDNAs of M195, a murine mAb that binds to the CD33 Ag on normal and leukemic myeloid cells, were cloned. The cDNAs were used in the construction of mouse/human IgG1 and IgG3 chimeric antibodies. In addition, humanized antibodies were constructed which combined the complementarity-determining regions of the M195 antibody with human framework and constant regions. The human framework was chosen to maximize homology with the M195 V domain sequence. Moreover, a computer model of M195 was used to identify several framework amino acids that are likely to interact with the complementarity-determining regions, and these residues were also retained in the humanized antibodies. Unexpectedly, the humanized IgG1 and IgG3 M195 antibodies, which have reshaped V regions, have higher apparent binding affinity for the CD33 Ag than the chimeric or mouse antibodies. |
| Keywords: |
nonhuman; mouse; animal; mice; molecular cloning; cloning, molecular; antibodies, monoclonal; immunoglobulin heavy chain; immunoglobulin variable region; amino acid sequence; molecular sequence data; recombinant fusion proteins; immunoglobulin g; plasmid; base sequence; antibody specificity; antigens, cd; immunoglobulin g1; immunoglobulin g3; sequence homology; immunoglobulin light chain; complementary dna; antibody affinity; antigens, differentiation, myelomonocytic; scatchard plot; chimeric antibody; lymphocyte antigen; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.
|
