Antigen choice in adoptive T-cell therapy of cancer

Immunotherapy of cancer through adoptive transfer of genetically engineered T-cells constitutes a more powerful strategy than attempts to mobilize the endogenous T-cell repertoire. Application of this technology in patients offers great opportunities towards a long-awaited breakthrough in cancer immunotherapy. However, recent findings in preclinical mouse models indicate that infusion of T-cells directed against tumor-associated auto-antigens can be associated with higher ‘on target’ toxicity than was anticipated on the basis of anti-tumor vaccination studies. Critical evaluation of candidate target antigens is required to ensure that T-cell receptor gene therapy will result in preferential attack of tumor cells in the absence of irreversible damage to vital somatic tissues.