A review of modifications to recombinant antibodies: attempt to increase efficacy in oncology applications.
Although monoclonal antibodies have high specificity, their usefulness in the clinic, especially against solid tumors, has been limited. This arises in part from the inability of antibody molecules to penetrate into the tumor and kill the tumor cells. In addition, natural cytotoxic effects of antibodies, mediated through complement or Fc receptors, may not be sufficient to kill malignant cells. This review will present some of the antibody modifications used to increase efficacy. Modified recombinant antibodies have been designed to be more cytotoxic (immunotoxins), to increase natural effector functions (bivalent antibodies, antibody-fusion molecules, multimeric antibodies, directed mutations in Fc region), or to pretarget cells for concentration of cytotoxic drugs. This review will also focus on engineering of smaller versions of antibodies that retain specificity (single chain Fvs, Fabs, Fab(2)s, minibodies, domain deleted antibodies) and have increased penetrability of solid tumors. Many of these antibody modifications may result in antigenic compounds which can limit repeat administration. Clinical experiences will be highlighted if information is available.
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IDEC Pharmaceuticals, 3010 Science Park Road, P.O. Box 919080, San Diego, CA 92191-9080, USA. mreff@idecpharm.com
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000592:standards* / Q000627:therapeutic use; D015195:Drug Design; D006801:Humans; D018796:Immunoconjugates / Q000493:pharmacokinetics / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy*; D015202:Protein Engineering; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D018796:Immunoconjugates; D011994:Recombinant Proteins