A review of modifications to recombinant antibodies: attempt to increase efficacy in oncology applications

Although monoclonal antibodies have high specificity, their usefulness in t he clinic, especially against solid tumors, has been limited. This arises i n part from the inability of antibody molecules to penetrate into the tumor and kill the tumor cells. In addition, natural cytotoxic effects of antibo dies, mediated through complement or Fc receptors, may not be sufficient to kill malignant cells. This review will present some of the antibody modifi cations used to increase efficacy. Modified recombinant antibodies have bee n designed to be more cytotoxic (immunotoxins), to increase natural effecto r functions (bivalent antibodies, antibody-fusion molecules, multimeric ant ibodies, directed mutations in Fc region), or to pretarget cells for concen tration of cytotoxic drugs. This review will also focus on engineering of s maller versions of antibodies that retain specificity (single chain Fvs, Fa bs, Fab(2)s. minibodies. domain deleted antibodies) and have increased pene trability of solid tumors. Many of these antibody modifications may result in antigenic compounds which can limit repeat administration, Clinical expe riences will be highlighted if information is available. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.