Therapeutic targeting of CD70 and CD27

ABSTRACT

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

KEYWORDS:

• Antibodies
• CD27
• CD70
• lymphoma
• regulatory T-cells
• tumor therapy

Article highlights

• CD27 activation efficiently costimulates T cells but chronic stimulation of CD27 results in immune suppression.

• CD70 is expressed by T- and B cells but also by T- and B-cell lymphomas and a considerable fraction of solid tumors.

• CD70 promotes expansion of intratumoral regulatory T cells.

• CD70 and CD27 have been successfully targeted in preclinical models of cancer, autoimmunity, and chronic viral infection.

• CD70- and CD27-specific antibodies are under investigation in clinical trials for the treatment of cancer.

This box summarizes key points contained in the article.

Declaration of interest

This work was supported by research grants from the Deutsche Forschungsgemeinschaft (DFG, grant WA 1025/24-1). The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.