Humanized anti-TAG-72 CC49 monoclonal antibodies are disclosed herein. The
antibodies include a light chain Complementarity Determining Region
(L-CDR)1, a L-CDR2, and a L-CDR3; and a heavy chain Complementarity
Determining Region (H-CDR)1, a H-CDR2, and a H-CDR3 from humanized
antibody HuCC49V10. The L-CDR1, L-CDR2, L-CDR3 are within a HuCC49V10
light chain framework region that includes the corresponding amino acid
from LEN at position 5, 19, 21, and 106 in the light chain. The H-CDR1,
H-CDR2, and H-CDR3 are within a heavy chain HuCC49V10 framework
comprising a human 21/28' CL residue at positions 20, 38, 48, 66, 67, 69,
and 80 in the heavy chain. These humanized CC49 antibodies retain binding
affinity for TAG-72 and have reduced immunogenicity, as compared to a
parental HuCC49V10 antibody. Methods are disclosed herein for using these
antibodies in the treatment or diagnosis of a tumor, such as a carcinoma,
expressing TAG-72.