The flexibility of plasmid design coupled with the technology of gene manipulation allows also "gene optimization." Indeed, the variable regions of the heavy (V H ) and light chain (V L ) of the tumor immunoglobulin, specific for the B-cell malignancies, can be readily cloned and combined into single-chain variable fragment (scFv) format, encoding a single polypeptide consisting of V H and V L genes linked together in frame by a short 15-amino acid linker [73] .