The present invention relates to novel antibodies,
antibody fragments and
antibody conjugates and single-chain immunotoxins reactive with human
carcinoma cells. More particularly, the antibodies, conjugates and single-chain immunotoxins of the invention include: a
murine monoclonal antibody, BR96; a human / murine
chimeric antibody, ChiBR96; a F(ab')2 fragment of BR96; ChiBR96-PE, ChiBR96-LysPE40, ChiBR96 F(ab')2-LysPE40 and ChiBR96 Fab'-LysPE40 conjugates and recombinant BR96 sFv-PE40
immunotoxin. These molecules are reactive with a
cell membrane antigen on the surface of human carcinomas. The BR96
antibody and its functional equivalents, displays a high degree of selectivity for
carcinoma cells and possess the ability to mediate antibody-dependent
cellular cytotoxicity and complement-dependent
cytotoxicity activity. In addition, the antibodies of the invention internalize within the
carcinoma cells to which they bind and are therefore particularly useful for therapeutic applications, for example, as the antibody component of antibody-
drug or antibody-
toxin conjugates. The antibodies also have a unique feature in that they are cytotoxic when used in the unmodified form, at specified concentrations.