Fig. 1.

Novel approaches for the generation of high-avidity CTL specific for tumour-associated antigens. Overview of four recently developed technologies to isolate high-affinity receptors specific for HLA class I presented peptide epitopes (HLA-A2 is shown because it is one of the most frequent class I alleles in humans). (a) and (b) take advantage of the TCR repertoire of healthy individuals or transgenic mice that are not tolerant to A2-presented peptide epitopes of tumour-associated antigens (TAA); (c) and (d) take advantage of in vitro mutagenesis and selection of high affinity TCRs (c) or high-affinity single chain antibodies specific for the peptide/HLA combination. (e) Strategies to transfer high avidity HLA-restricted receptors into patient T cells or stem cells to produce tumour-reactive T cells.