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Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121
The antitumor effects of an unmodified murine monoclonal antibody, BR96, were examined in nude mice bearing human lung adenocarcinoma xenografts. BR96, a murine IgG3 that internalizes and is cytotoxic to cells expressing the antigen in vitro, also elicits strong antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity effector functions. Its in vivo antitumor effects were compared with those of its F(ab')2 fragments, a mouse-human chimeric form, and an IgG1 class switched variant of the original (IgG3) BR96. Antitumor effects were observed with antigen-positive tumor lines (but not with tumors which did not bind with BR96) and correlated with the levels of antigen expression as detected in vitro. The chimeric form of BR96 gave the strongest antitumor effects, followed by the murine IgG3, while limited effects were seen with the IgG1 and with F(ab')2 fragments of BR96, indicating that Fc-dependent host effector functions are primarily responsible for its in vivo activity. The antitumor effects observed were modest unless the antibody treatment was started on the day following tumor grafting.
1 Supported by Bristol-Myers Squibb Pharmaceutical Research Institute.
2 To whom requests for reprints should be addressed, at Bristol-Myers Squibb Pharmaceutical Research Institute, 3005 First Avenue, Seattle, WA 98121.
Received 11/12/91. Accepted 4/ 6/92.
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