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Towards a favorable systemic radio-immunotherapy target

Date:
October 15, 2015
Source:
World Scientific
Summary:
Survival probability of Hodgkin's lymphoma (HL) has improved significantly over the past two decades. Monoclonal antibodies against targeted proteins on Reed-Sternberg cells in HL though a popular choice for immunotherapy have yet to demonstrate complete responses. In a new study, researchers have considered the ripple effects of 90Y-daclizumab, a drug which targets CD25+ tumor cells in Hodgkin's Lymphoma during radio-immunotherapy. The results demonstrated 30.4 percent complete and 19.6 percent partial responses in HL patients.
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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.


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Materials provided by World Scientific. Note: Content may be edited for style and length.


Journal Reference:

  1. John E. Janik, John C. Morris, Deirdre O’Mahony, Stefania Pittaluga, Elaine S. Jaffe, Christophe E. Redon, William M. Bonner, Martin W. Brechbiel, Chang H. Paik, Millie Whatley, Clara Chen, Jae-Ho Lee, Thomas A. Fleisher, Maggie Brown, Jeffrey D. White, Donn M. Stewart, Suzanne Fioravanti, Cathryn C. Lee, Carolyn K. Goldman, Bonita R. Bryant, Richard P. Junghans, Jorge A. Carrasquillo, Tat’Yana Worthy, Erin Corcoran, Kevin C. Conlon, Thomas A. Waldmann. 90Y-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; 201516107 DOI: 10.1073/pnas.1516107112

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World Scientific. "Towards a favorable systemic radio-immunotherapy target." ScienceDaily. ScienceDaily, 15 October 2015. <www.sciencedaily.com/releases/2015/10/151015115752.htm>.
World Scientific. (2015, October 15). Towards a favorable systemic radio-immunotherapy target. ScienceDaily. Retrieved May 23, 2017 from www.sciencedaily.com/releases/2015/10/151015115752.htm
World Scientific. "Towards a favorable systemic radio-immunotherapy target." ScienceDaily. www.sciencedaily.com/releases/2015/10/151015115752.htm (accessed May 23, 2017).

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