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 Blood, 1 October 2005, Vol. 106, No. 7, pp. 2287-2294.
Prepublished online as a Blood First Edition Paper on June 16, 2005; DOI 10.1182/blood-2004-11-4558.

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Submitted December 3, 2004
Accepted May 25, 2005

Oncolytic measles virus in cutaneous T-cell lymphomas mount anti-tumor immune responses in vivo and target interferon resistant tumor cells

Lucie Heinzerling, Valerie Kunzi, Patrick A Oberholzer, Thomas Kundig, Hussein Naim, and Reinhard Dummer*

Department of Dermatology and Allergy, Charite - University Hospital, Berlin, Germany; Department of Dermatology, University Hospital Zurich, Zurich, Switzerland
Berna Biotech AG, Bern, Switzerland
Department of Dermatology, University Hospital Zurich, Zurich, Switzerland

* Corresponding author; email: reinhard.dummer{at}usz.ch.

Some cutaneous T-cell lymphomas (CTCLs) clonal T-cells are deficient in interferon signaling, making them promising targets for viral oncolysis. We evaluated cytopathic effects of measles virus (MV) in CTCL . CTCL cell lines and infiltrating lymphocytes in CTCL expressed MV receptors CD150 and CD46. In a phase I dose escalation trial a total of 16 injections of live MV, Edmonston-Zagreb vaccine strain, were given intratumorally to five patients with CTCL. Patients had anti-measles serum antibodies and were pretreated with interferon-alpha in order to prevent uncontrolled virus spread. The well tolerated treatment with MV resulted in clinical responses. Evaluation of biopsies, before and at 11 days after injection, by immunohistochemistry and RT-PCR demonstrated local viral activity with positive staining for MV NP protein, an increase of the IFN-{gamma}/CD4 and IFN-{gamma}/CD8 mRNA ratio and a reduced CD4/CD8 ratio. All patients demonstrated an increased anti-measles antibody titer after therapy. The data demonstrate that CTCL are promising targets for a MV based oncolytic therapy.


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