Programmed cell death 1 (PDCD1, best known as PD-1) is a central negative regulator of effector T cells that is involved in the etiology of chronic inflammatory conditions, viral diseases, and cancer. We have recently sought to improve T-cell functions by means of a novel chimeric co-stimulatory molecule that could divert the negative signals normally transmitted by PD-1 into positive ones. Human T cells transduced to express a fusion protein encompassing the extracellular domain of PD-1 and the intracellular portion of the co-stimulatory molecule CD28, which we named PD-1/28, exhibited an increase in cytokine secretion, the upregulation of activation markers, an improved proliferative potential and superior antineoplastic activity in xenograft models of human melanoma.
Keywords: Adoptive T cell transfer; CD28; PD1; T-cell engineering; immunotherapy.