Therapeutic targeting of CD70 and CD27

CD70 and CD27 constitute a ligand-receptor pair of the TNF ligand and receptor family which is of major importance for T-cell costimulation. In healthy individuals CD70 expression is restricted to activated T-cells, certain subsets of immune cells and to epithelial cells of the thymic medulla. CD27 is expressed by naïve and memory T-cells and certain types of immune cells. Strikingly, CD70 is also often highly expressed on T- and B-cell lymphomas and on a considerable fraction of solid tumors.

Based on a brief description of the signaling mechanisms and immune regulatory activities of CD70 and CD27, this review is focused on strategies and concepts that exploit the function and expression pattern of these molecules for therapeutic purposes.

Therapeutic strategies have been developed that either aim to trigger or inhibit CD27 activity or solely use CD70 as a tumor marker. Some of these strategies are currently under consideration in clinical trials and have shown a good safety profile. The identification of biomarkers and stratification concepts is now important to ensure that a chosen CD70/CD27 targeting strategy fits optimally to the dominant function(s) of CD70 and CD27 in the corresponding individual case.