Adoptive cancer immunotherapy using genetically engineered designer T-cells: First steps into the clinic

Abstract

The treatment of patients with cancer using passive vaccination with antibodies has been demonstrated to be a promising option, particularly for 'soft tumors', most likely because of their greater accessibility compared with bulky solid tumors. While effector T-cells are efficient in the rejection of large organs and foreign tissues, the wide application of tumor-specific T-cells for cancer therapy has been limited by the inherent restriction of T-cell recognition to self antigens, and the difficulty in obtaining sufficient numbers of such cells with defined specificity. Advances in gene transfer and cell therapy have enabled the genetic modification of T-cells by the ectopic expression of predefined, specific receptor genes that redirect such 'designer cells' to any target of interest. This review discusses two approaches to applying redirected T-cells for adoptive cancer immunotherapy: the 'T-body' approach, which employs chimeric receptors with tumor-specific antibody-derived specificity, and the use of transgenes encoding tumor-specific T-cell receptors. Particular emphasis is placed on recent attempts using these approaches in the treatment of patients with cancer.