Molecular engineering to improve antibodies' anti-lymphoma activity

Best Pract Res Clin Haematol. 2011 Jun;24(2):217-29. doi: 10.1016/j.beha.2011.03.004. Epub 2011 May 7.

Abstract

The human/mouse chimeric CD20 antibody rituximab has significantly improved the survival of lymphoma patients. However, translational research into pharmacology and effector mechanisms of rituximab has identified several limitations of this prototypic antibody. For example, humanized or fully human next-generation antibodies demonstrated reduced immunogenicity, which may translate into improved applicability in certain patient populations. Furthermore, novel technologies of antibody engineering offer the potential to tailor antibody effector functions. Here, glyco- or protein engineering of antibodies' Fc region has demonstrated promising activity in preclinical models. However, these novel molecules are still in early phases of clinical development, and data from on-going and future studies will determine whether promising preclinical results will indeed translate into improved drugs for the treatment of lymphoma patients.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Murine-Derived / chemistry
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • Antigens, CD20 / immunology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • Immunity, Cellular
  • Immunity, Humoral
  • Immunoglobulin Fc Fragments / chemistry*
  • Immunoglobulin Fc Fragments / genetics
  • Immunoglobulin Fc Fragments / pharmacology
  • Immunoglobulin Isotypes / chemistry*
  • Immunoglobulin Isotypes / genetics
  • Immunoglobulin Isotypes / pharmacology
  • Immunotherapy*
  • Lymphoma, Follicular / genetics
  • Lymphoma, Follicular / immunology*
  • Lymphoma, Follicular / pathology
  • Lymphoma, Follicular / therapy
  • Mice
  • Models, Animal
  • Mutation
  • Primates
  • Rituximab
  • Species Specificity

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD20
  • Immunoglobulin Fc Fragments
  • Immunoglobulin Isotypes
  • Rituximab