Anti-tumour antibodies can target treatment and imaging agents selectively to cancer but have effector or linking regions that are not required for antigen recognition antibodies, at 27 kDa, are less than onefifth of the molecular mass of an IgG antibody. They penetrate better into tumours while retaining full antigen specificity [2]. ScFvs consist of the antibody variable heavy (VH) and variable light (VL) regions linked with a short synthetic peptide to form a single molecule of 27 kDa [3]. ScFvs minimize immunogenicity by avoiding the administration of protein not required for antigen binding. High ratios of tumour to normal tissue are reported with scFvs in animal models but with a lower total amount of antibody in tumour [4-61. T o attain high concentrations of antibody at the tumour site it is crucial for scFvs to have high affinities because they are only monovalent for antigen.Although great diversity exists in the antibody repertoire it has not been possible to examine more than 102-103 clones by using hybridoma technology. This limits the ability to generate high-affinity scFvs from conventional monoclonal antibodies because less than 0.1 % of an antibody repertoire can be examined by screening. In combinatorial antibody libraries [ 71 expressed in filamentous bacteriophage [XI, cloned scFvs are generated directly from B-cells. These cDNA libraries contain VH and VL genes extracted separately from the B-cell, amplified by PCR and randomly recombined with a flexible linker to form scFvs. This augments diversity by creating VH and VL pairings that do not occur naturally in B-cells. Some original high-affinity V gene pairings from immunized animals might be lost but the creation of novel pairings might outweigh this, especially if many of the original clones react with a limited number of immunodominant epitopes.
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