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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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GENE THERAPY
Oncolytic measles virus in cutaneous T-cell lymphomas mounts antitumor immune responses in vivo and targets interferon-resistant tumor cells
Lucie Heinzerling,
Valerie Künzi,
Patrick A. Oberholzer,
Thomas Kündig,
Hussein Naim, and
Reinhard Dummer
From the Department of Dermatology, University Hospital Zurich, Zurich, Switzerland; and Berna Biotech AG, Bern, Switzerland.
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 1 dose escalation trial a total of 16 injections of live MV, Edmonston-Zagreb vaccine strain, were given intratumorally to 5 patients with CTCL. Patients had antimeasles-serum antibodies and were pretreated with interferon- 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 reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated local viral activity with positive staining for MV nucleoprotein (NP), an increase of the interferon  (IFN-)/CD4 and IFN-/CD8 mRNA ratios and a reduced CD4/CD8 ratio. All patients demonstrated an increased antimeasles antibody titer after therapy. The data demonstrate that CTCLs are promising targets for an MV-based oncolytic therapy.
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