Co-stimulatory Immune Checkpoint Targets

CD27 is a lymphocyte-specific member of the tumour necrosis factor receptor (TNF-R) family, expression of which is tightly regulated during T-cell ontogeny. Recently, the ligand for CD27 was identified and was shown to be identical to CD70, a novel member of the TNF family. Functional experiments show that the interaction between CD27 and its ligand generates a co-stimulatory signal for T-cell activation.

In 1994, OX40L was identified on an EBV-transformed B cell line with low-level expression on activated T cells. This ligand for OX40 is a type II transmembrane protein and bothmRNA and protein are markedly induced in human Tcell leukaemia virus 1-infected cells. OX40L is expressed in trimeric form and binds three OX40 molecules with high affinity and slow dissociation. After it was cloned, OX40L was shown to increase T cell proliferation in response to a variety of standard stimuli.