Engineering therapeutic monoclonal antibodies

Research output: Contribution to journalReview article

79 Scopus citations

Abstract

During last two decades, the chimerization and humanization of monoclonal antibodies (mAbs) have led to the approval of several for the treatment of cancer, autoimmune diseases, and transplant rejection. Additional approaches have been used to further improve their in vivo activity. These include combining them with other modalities such as chemotherapy and redesigning them for improved pharmacokinetics, effector function, and signaling activity. The latter has taken advantage of new insights emerging from an increased understanding of the cellular and molecular mechanisms that are involved in the interaction of immunoglobulin G with Fc receptors and complement as well as the negative signaling resulting from the hypercrosslinking of their target antigens. Hence, mAbs have been redesigned to include mutations in their Fc portions, thereby endowing them with enhanced or decreased effector functions and more desirable pharmacokinetic properties. Their valency has been increased to decrease their dissociation rate from cells and enhance their ability to induce apoptosis and cell cycle arrest. In this review we discuss these redesigned mAbs and current data concerning their evaluation both in vitro and in vivo.

Original languageEnglish (US)
Pages (from-to)9-27
Number of pages19
JournalImmunological Reviews
Volume222
Issue number1
DOIs
StatePublished - Apr 1 2008

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Keywords

  • Effector function
  • Fc
  • Monoclonal antibody
  • Pharmacokinetics
  • Tumors

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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