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KMID : 0357119950170010011
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Korean Journal of Immunology
1995 Volume.17 No. 1 p.11 ~ p.16
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Immunogenicity of Murine Variable and Complementarity-determining Region of Humanized Antibodies in Rabbits as an Animal Model
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김윤규
진병래/박성섭/정홍근/김희철/한문희/홍효정
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Abstract
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to predict the imnogenicity of murine variable region and complementarity-determining region (CDR0 of chimeric and humanized antibody, random-bred rabbits were used as an animal model. Radbits were injected intravenously with mouse H8 monoclonal
antibody 9mAb), which is specific for the pre-S2 of Hepatitis B virus (HBV), using a dose and schedule comparable to human trials, and the specificity of the rabbit antibody was assayed by a modified ELISA followed by competitive ELISA using
polyclonal
mouse IgG, chimeric antibody (H69K) and humanized antibody (Z6B). Rabbit anti-H8 antibody of primary immune response ws inhibited 87 - 92% by polyconal mouse IgG and 3 - 21% by chimeric H60K while the rabbit antibody of secomndary response was
rabbit
antibody response was inhibited 85-87% by polyconal mouse IgG, 5-9% by chimeric H69K and 2-7%d humanized Z6B. The results suggest that rabbit immune response to the mouse mAb H8 was mostly directed by the constant region and the CDR in the
variable
region. This animal model system could mimic the intensity and specificity of human immune response to murine varible region and CR, and thus could be used to identify murine monoclonal antivodies of low immunogenicity that would be good
candidates
for
genetically engineered antiodies.
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