ANTI-EGFRVIII SCFVS WITH IMPROVED CYTOTOXICITY AND YIELD, IMMUNOTOXINS BASED THEREON, AND METHODS OF USE THEREOF

摘要

The invention provides antibodies for a mutant form of the epidermal growth factor receptor known as EGFRvIII. This mutant is found only or primarily on the surface of glioblastoma cells, and on cells of breast, ovarian and non-small cell lung carcinomas. The antibodies provided by the invention have higher affinity for EGFRvIII, and form immunotoxins with higher cytotoxicity and yield, than prior art antibodies, including the scFv designated MR1. In particular, the invention provides an antibody, designated MR1-1, which mutates MR1 in the CDR3 of the VH and VL chains to provide an antibody with especially good cytotoxicity. The invention provides additional antibodies in which MR1 is mutated in the CDR1 and 2 of VH or VL, or both, with better binding to EGFRvIII than that of the parental MR1 antibody.