Towards a favorable systemic radio-immunother target

The IL-2 receptor α subunit, CD25 is commonly expressed in T-regulatory (Treg) cells and a small subset of Reed-Sternberg cells in Hodgkin's Lymphoma (HL). Normal resting cells do not express CD25. An article published by Janik et. al 2015 (PNAS) stated that the predominant motivation to engage anti-CD25 in HL radioimmunotherapy is the expression of CD25 on T cells rosetting around Reed-Sternberg cells. Thereby, non-CD25 expressing tumor cells can also be killed during the crossfire of the battlefield when a high radiation dose is delivered.

^90Y has a high β-energy emission, with a mean path length of 5mm and a maximum of 11mm. In Janik's study, the two clinical studies of relapsed-HL consecutive patients who were studied between April 2003 and October 2007 (n=30); between November 2009 and June 2014 (n=16) used daclizumab, a humanized anti-Tac, i.e. anti-CD25. The recruited patients received ^90Y-daclizumba every 6-10 week and with a maximum cap of seven doses.

The clinical study presented encouraging results of ^90Y-daclizumab radioimmunotherapy in relapsed HL patients: 30.4% complete responses and 19.6% partial responses. The patients' follow-up responses showed minor toxicity - thrombocytopenia and granulocytopenia.

However, six of the 30 patients in the first study presented myelodysplastic syndrome (MDS). Though MDS is a concern in oncology studies, the study is unable to draw supportive conclusions on whether ^90Y-daclizumab may trigger MDS among HL patients with different medical histories and whom have received different combinations of onco-therapies.

More information:
John E. Janik et al. Y-daclizumab, an anti-CD25 monoclonal antibody, provided responses in 50% of patients with relapsed Hodgkin’s lymphoma , Proceedings of the National Academy of Sciences (2015). DOI: 10.1073/pnas.1516107112

Provided by World Scientific Publishing