Explain the different approaches to antibody humanization.

Antibody humanization reduces immunogenicity of non-human antibodies for therapeutic use. Approaches include: 1) Chimeric antibodies - replace murine constant regions with human sequences while retaining murine variable regions; 70% human, reduced immunogenicity but still foreign V regions. 2) CDR grafting - transfer only CDRs from murine antibody onto human framework; may require back-mutations in framework to maintain binding. 3) Resurfacing - replace surface-exposed framework residues with human sequences while keeping buried residues. 4) SDR transfer - graft only Specificity Determining Residues (subset of CDRs). 5) Fully human antibodies - from transgenic mice with human antibody genes (XenoMouse) or phage/yeast display libraries. Each level of humanization balances reduced immunogenicity against maintained binding affinity and function.