HUMANIZED ANTI TAC ANTIBODY THERAPY IN LEUKEMIA/ LYMPHOM

Beth Israel Deaconess Medical Center, Boston MA

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Abstract

Cancer therapy with monoclonal antibodies has been hampered by two major obstacles: 1) foreign proteins such as antibodies are neutralized when patients develop an antiglobulin response and 2) most MAb are of mouse origin and are often less efficient at recruiting human effector functions. As one approach to these problems, human-mouse chimeric and "hyperchimeric" antibodies have been prepared by genetic engineering. Potential advantages are: 1) "Humaniztion reduces the antigenic target on the antibody that is the stimulus for neutralizing antiglobulin responses. 2) Supplying human constant domains to the antibody may dramatically improve the recruitment of host cellular killing that may be important to the tumoricidal activity of the antibody in vito and which is often weak or absent in the parental rodent antibody. 3) Human lgG constant domains could confer longer in vivo half-life of the order of 23 dys for human lgG in man versus the 1-3 day t 1/12 of murine antibody in humans.