Historical perspectives and future directions of gene-modified T-cell therapy

Adoptive immunotherapy using genetically modified T-cells is an emerging and promising treatment modality for various malignant diseases. The technology involves engineering of T-cells armed with well-characterized receptors such as T-cell receptors or chimeric antigen receptors. The latter is comprised of antibody/ligand and intracellular signaling domains. These molecules can be further modified to enhance their affinity, specificity, and several other functions. The success of adoptive immunotherapy is rooted in the application of extensive insights derived from allogeneic hematopoietic stem cell transplantations (HSCT). Herein, the historical perspectives of gene-modified T-cell therapy are discussed by comparison with the evolution of allogeneic HSCT. Furthermore, the prospects for the development and improvement of these powerful therapeutic methods are also highlighted.