Recombinant measles virus induces cytolysis of cutaneous T-cell lymphoma in vitro and in vivo.
Measles virus (MV) has shown promise as an oncolytic virus in the treatment of different tumor models for human B-cell lymphoma, multiple myeloma, ovarian cancer, and glioma. We have shown that, in a phase I clinical trial, MV vaccine induces tumor regression in cutaneous T-cell lymphoma (CTCL) patients. Here, we investigated in detail, the effect of recombinant MV (rMV) vaccine strain in CTCL cell cultures, and in vivo in established CTCL xenografts in nude mice. The susceptibility of three CTCL cell lines, originating from patients, to rMV was tested by determination of cell surface expression of MV receptors. All cell lines expressed the receptors CD150 and CD46 and were easily infected by rMV and induced complete cell lysis. The cytoreductive activity was apparent in cells forming aggregates, indicating a cell-to-cell spread of MV and cytolysis owing to virus infection. Intratumoral (i.t.) injection of rMV, expressing enhanced green fluorescent protein induced complete regression of large established human CTCL tumors in nude mice, whereas tumors with control treatment progressed exponentially. Immunohistochemical analysis of tumor biopsies, after i.t. treatment, for MV-NP protein complex demonstrated replication of MV within the tumors. The data demonstrate the potential of MV as a therapeutic agent against CTCL.
Künzi
Valerie
V
Berna Biotech Ltd, Bern, Switzerland.
Oberholzer
Patrick A
PA
Heinzerling
Lucie
L
Dummer
Reinhard
R
Naim
Hussein Y
HY
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D019496:Cancer Vaccines / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D006801:Humans; D016410:Lymphoma, T-Cell, Cutaneous / Q000737:chemistry / Q000628:therapy*; D008458:Measles Vaccine / Q000627:therapeutic use*; D008459:Measles virus / Q000235:genetics / Q000502:physiology; D051916:Membrane Cofactor Protein / Q000032:analysis; D051379:Mice; D008819:Mice, Nude; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000235:genetics / Q000502:physiology; D011956:Receptors, Cell Surface / Q000032:analysis; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D014775:Virus Activation; D023041:Xenograft Model Antitumor Assays
D015703:Antigens, CD; D019496:Cancer Vaccines; D008458:Measles Vaccine; D051916:Membrane Cofactor Protein; D011956:Receptors, Cell Surface; C000604059:SLAMF1 protein, human; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1