Reshaping antibodies for therapy

Contents

• 1. Introduction
• 2. Current strategies in designing reshaped antibody variable regions
• 3. Future Strategies for Reshaping
  • 3.1 Somatic mutations in the acceptor V region frameworks
  • 3.2 Germline V region genes as a source of acceptor frameworks
  • 3.3 Germline V region genes and the "Best Fit" strategy
  • 3.4 Influence of genetic conservation on the choice of germline V region acceptor genes
• 4. Further reduction of potential immunogenicity
• 5. Prospects for producing non-immunogenic monoclonal antibodies
• 6. Conclusions
• 7. References
• Figures
  • Figure 1. Reshaping of the CAMPATH-1 Variable regions V_H and V_L
  • Figure 2. Reshaping of the rat CD4 antibody CAMPATH-9
  • Figure 3. Anti-Tac J_H Region Comparisons
  • Figure 4. Human J_H segment amino acid sequences
  • Figure 5. Sequence comparisons of humanized antibodies with the chosen frameworks and closest matches
  • Figure 6. YTH 12.5 J_H Region comparisons
  • Figure 7. Comparison of CDRs 1 and 2 of the rat YTH 12.5 and the human V_H26 V_H regions
  Tables
  • Table 1. Human acceptor V regions used during the humanization of various monoclonal antibodies
  • Table 2. Murine - Human V_H region comparisons for CAMPATH-1H, anti-Tac and OKT3
  • Table 3. Comparison of V_H26 to other Homologous Human V_HIII Germline Genes

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