Out of the bitter came forth sweet: Activating CD28-dependent co-stimulation via PD-1 ligands.
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.
Laboratory of Tumor Immunology and Immunotherapy; The Goodman Faculty of Life Sciences; Bar-Ilan University; Ramat Gan, Israel.
Chen
C
Ankri
Laboratory of Tumor Immunology and Immunotherapy; The Goodman Faculty of Life Sciences; Bar-Ilan University; Ramat Gan, Israel.
Cyrille J
CJ
Cohen
Adoptive T cell transfer; CD28; PD1; T-cell engineering; immunotherapy