New publication shows: CD70/CD27 signaling pathway is a key driver of myeloma development — unlocking potential for novel therapies

Multiple myeloma is a malignant disease of the plasma cells and, despite significant therapeutic advances, is still considered incurable. Almost all patients experience a recurrence during the course of the disease, which often only responds inadequately to established therapies. In some patients, there is also an extramedullary spread of malignant plasma cells, which is associated with a significantly worse prognosis and shorter overall survival.

In the present study, we demonstrate that the CD70/CD27 signalling axis plays a central role in the development, progression and dissemination of multiple myeloma. The co-expression of the ligand-receptor pair CD70/CD27 on myeloma cells leads to the autonomous activation of this signalling axis and thereby promotes both the proliferation and the spread of tumour cells. In advanced, extramedullary disease stages, a pronounced overexpression of CD70 was observed.

Our preclinical investigations of CD70-positive myeloma cell lines and CD70-expressing xenograft models demonstrate that both genetic silencing (knockout) of CD70 and its targeted blockade using monoclonal anti-CD70 antibodies can significantly inhibit tumour growth.

In summary, the CD70/CD27 signalling axis is a promising therapeutic target, particularly for advanced and treatment-resistant stages of multiple myeloma.

Forster S, Reinhardt C, Boy M, Wegmüller A, Hinrichsen A, Schürch CM, Brühl FK, Fend F, Tzankov A, Kronig MN, Römmele M, Glück A, Lüscher B, Legros M, Bacher U, Seipel K, Pabst T, Radpour R, Riether C, Ochsenbein AF. CD70/CD27 signaling promotes the pathogenesis of multiple myeloma and represents a promising therapeutic target. Leukemia. 2026 Mar 23. doi: 10.1038/s41375-026-02899-1. PMID: 41872502.