CD28

aka CD28 molecule, CD28 costimulatory receptor

CD28 is the second signal a T cell needs before it attacks. Many CAR-T cells carry a piece of CD28 inside them to fire harder, ipilimumab works by stopping CTLA-4 from hogging CD28's partners, and a new bispecific antibody presses CD28 directly on T cells that are already bound to prostate cancer cells.

CD28 (chromosome 2q33.2) is the T-cell receptor for CD80 and CD86 that drives T-cell activation, proliferation and survival: it amplifies T-cell receptor signals and delivers its own, recruiting PKC-theta and GRB2 to activate NF-kappa-B through PI3K/AKT-dependent and independent routes and raising proliferation and IL-2 production in CD4 and CD8 T cells (UniProt P10747). In OnCo it appears three ways: as the costimulatory domain built into the CD19 CAR-T products axicabtagene and brexucabtagene (the lisocabtagene record notes slower expansion and less CRS and ICANS than CD28-based products); as the receptor CTLA-4 outcompetes for B7 ligands, the priming step ipilimumab releases; and as the T-cell arm of JNJ-87189401, a PSMA x CD28 costimulatory bispecific in phase 3 for prostate cancer.

CD28: what it is and how drugs act on it · animated schematic, not to scale

Target · the protein and the cell it sits on
Drug · antibody, small molecule, cell or radioligand
Effect · signal, damage or kill

In plain words · CD28 is the second signal a T cell needs before it attacks. Many CAR-T cells carry a piece of CD28 inside them to fire harder, ipilimumab works by stopping CTLA-4 from hogging CD28's partners, and a new bispecific antibody presses CD28 directly on T cells that are already bound to prostate cancer cells.

1 · What it is
CD28 is the second signal a T cell needs before it attacks. Many CAR-T cells carry a piece of CD28 inside them to fire harder, ipilimumab works by stopping CTLA-4 from hogging CD28's partners, and a new bispecific antibody presses CD28 directly on T cells that are already bound to prostate cancer cells.
2 · What goes wrong in cancer
CD28 is constitutively expressed on T cells, and CD80 on antigen-presenting cells is its primary auxiliary signal (UniProt P33681).
3 · How drugs use it
1 product aims at CD28: bispecific antibodies. Because it sits on the outside of the cell, it can be reached from the bloodstream: antibodies flag the cell, ADCs deliver a toxin, radioligands deliver radiation, and CAR-T or bispecifics bring a T cell.

Full dossier: hotspots, trials, resistance, assays, models, open questions →

External identifiers

CD28HGNCEnsemblUniProtAlphaFold DBOpen TargetsCIViCOncoKBCOSMICcBioPortalDepMapHuman Protein AtlasNCBI GeneOMIM

Biology

CD28 is constitutively expressed on T cells, and CD80 on antigen-presenting cells is its primary auxiliary signal (UniProt P33681). The bispecific approach costimulates only T cells whose other arm is already engaged with a tumour antigen, here PSMA.

Where it is found