CD27 is a type I transmembrane protein expressed on naïve and activated T cells, natural killer (NK) cells, and activated B cells . Its ligand, CD70, triggers signaling pathways that enhance T cell proliferation, cytokine production, and long-term immunity . CD27 antibodies are engineered to either agonize or block this pathway, making them promising candidates for immunotherapy in oncology and infectious diseases .
CD27 antibodies function by binding to CD27, mimicking or inhibiting its interaction with CD70. Key mechanisms include:
Co-stimulation of T cells: Agonist antibodies (e.g., 1F5/CDX-1127) amplify TCR signaling, leading to NF-κB and MAPK8/JNK activation, which drives T cell clonal expansion and survival .
Fc receptor dependence: Agonist activity requires Fcγ receptor cross-linking, as demonstrated by reduced efficacy in aglycosylated antibody variants .
Apoptosis regulation: CD27-binding protein SIVA can induce apoptosis, but agonist antibodies primarily override this effect to promote immune activation .
Studies in transgenic mice and humanized models highlight the therapeutic potential of CD27 antibodies:
The lead candidate, CDX-1127 (1F5), is a fully human IgG1 agonist antibody in Phase I trials for advanced cancers . Preclinical data show:
Synergy with vaccines: Combined use with protein vaccines amplifies CD8+ T cell responses .
Durable immunity: Treated mice developed protective memory against tumor rechallenge .
CD27 antibodies have broad therapeutic implications:
Antitumor immunity: Enhanced cytotoxic T cell activity against lymphoma, melanoma, and thymoma .
Antiviral responses: CD27 costimulation improves CD8+ T cell memory in murine viral models .
Autoimmune modulation: Potential to suppress pathological T cell activation (under investigation) .
The anti-CD27 antibody ab175403 (Abcam) is widely used in research:
| Parameter | Details |
|---|---|
| Host species | Rabbit |
| Reactivity | Human, Mouse, Rat |
| Applications | WB (1:3000), IHC (1:100), IF (1:100) |
| Key validation | Bands at ~29 kDa in Raji, Jurkat, and mouse thymus lysates (Western blot) |
| Tissue staining | Localized in thymus and spleen (human, mouse, rat) |