Oncolytic measles virus in cutaneous T-cell lymphomas mounts antitumor immune responses in vivo and targets interferon-resistant tumor cells.
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-alpha 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 gamma (IFN-gamma)/CD4 and IFN-gamma/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.
Heinzerling
Lucie
L
Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
Künzi
Valerie
V
Oberholzer
Patrick A
PA
Kündig
Thomas
T
Naim
Hussein
H
Dummer
Reinhard
R
D015703:Antigens, CD; D001706:Biopsy; D015704:CD4 Antigens / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D016827:CD8 Antigens / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002469:Cell Separation; D018076:DNA, Complementary / Q000378:metabolism; D004351:Drug Resistance; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods*; D007249:Inflammation; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics; D007372:Interferons / Q000494:pharmacology*; D008214:Lymphocytes / Q000166:cytology / Q000821:virology; D016399:Lymphoma, T-Cell / Q000276:immunology / Q000628:therapy* / Q000821:virology; D008459:Measles virus / Q000235:genetics*; D009698:Nucleoproteins / Q000235:genetics; D050504:Oncolytic Viruses / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D013997:Time Factors; D019076:Transgenes
D015703:Antigens, CD; D015704:CD4 Antigens; D016827:CD8 Antigens; D018076:DNA, Complementary; D006023:Glycoproteins; D007136:Immunoglobulins; D016898:Interferon-alpha; D009698:Nucleoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C000604059:SLAMF1 protein, human; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D007371:Interferon-gamma; D007372:Interferons