Oncolytic measles virus in cutaneous T-cell lymphomas mounts antitumor immune responses in vivo and targets interferon-resistant tumor cells.

@article{Heinzerling2005OncolyticMV,
  title={Oncolytic measles virus in cutaneous T-cell lymphomas mounts antitumor immune responses in vivo and targets interferon-resistant tumor cells.},
  author={Lucie Heinzerling and Valérie Künzi and Patrick Antony Oberholzer and Thomas M K{\"u}ndig and Hussein Y. Naim and Reinhard Dummer},
  journal={Blood},
  year={2005},
  volume={106 7},
  pages={
          2287-94
        }
}
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… 
View on PubMed
ashpublications.org
166 Citations
Highly Influential Citations
6
Background Citations
63
Methods Citations
11
Results Citations
4

Figures and Tables from this paper

166 Citations

Recombinant measles virus induces cytolysis of cutaneous T-cell lymphoma in vitro and in vivo.

The data demonstrate the potential of MV as a therapeutic agent against CTCL and investigate in detail, the effect of recombinant MV (rMV) vaccine strain in CTC lysis cell cultures, and in vivo in established C TCL xenografts in nude mice.

Phase II Clinical Trial of Intratumoral Application of TG1042 (Adenovirus-interferon-γ) in Patients With Advanced Cutaneous T-cell Lymphomas and Multilesional Cutaneous B-cell Lymphomas.

Cutaneous lymphomas, in particular B-cell lymphomas with high objective response rates, seem to be excellent targets for this type of immunotherapy, with well tolerated treatment and systemic immune activation after intralesional therapy.

Oncolytic measles virus and mesenchymal stromal cells: A therapeutic model and a dissection of mechanisms of action

It is demonstrated that human bone marrow-derived mesenchymal stromal cells (BM-MSCs) can be used effectively as virus delivery vehicles, permitting ex-vivo cellular virus loading and intracellular virus amplification, delivery of virus to distant sites of disease following systemic infusion, and virus hand-off to precursor B lineage ALL cell targets in the presence of pre-existing anti-MV antibodies.

Lymphoma chemovirotherapy: CD20-targeted and convertase-armed measles virus can synergize with fludarabine.

Combination chemotherapy regimen incorporating CD20 antibodies are commonly used in the treatment of CD20-positive non-Hodgkin's lymphoma (NHL). Fludarabine phosphate (F-araAMP), cyclophosphamide,…

Oncolytic virotherapy-mediated anti-tumor response: a single-cell perspective.

Measles virotherapy in a mouse model of adult T-cell leukaemia/lymphoma.

MV therapy could be a promising therapy for generalized lymphoproliferative disease in mice with a high tumour burden, and therapy with the vaccine-related strain MV-NSE significantly increased survival beyond any other single treatment tested previously using this model.

Measles virus induces oncolysis of mesothelioma cells and allows dendritic cells to cross-prime tumor-specific CD8 response.

The antineoplastic potential of a new oncolytic viral agent, a live-attenuated measles virus (MV) strain derived from the Edmonston vaccine lineage (Schwarz strain), is investigated and it is shown that MV Schwarz strain induced apoptotic cell death of infected mesothelioma cells, which were efficiently phagocytosed by dendritic cells (DC).

Mantle cell lymphoma salvage regimen: synergy between a reprogrammed oncolytic virus and two chemotherapeutics

These studies document a reprogrammed oncolytic virus, consolidating the effects of two chemotherapeutics, a concept well suited for a phase I clinical trial for MCL patients for whom conventional therapies have failed.

Human mesenchymal stromal cells deliver systemic oncolytic measles virus to treat acute lymphoblastic leukemia in the presence of humoral immunity.

Human bone marrow-derived mesenchymal stromal cells were used to efficiently deliver MV in a systemic xenograft model of precursor B-lineage-ALL and successful MV treatment was completely abrogated by passive immunization with high-titer human anti-MV antibody.

Specific elimination of CD133+ tumor cells with targeted oncolytic measles virus.

It is indicated that CD133-targeted measles viruses selectively eliminate CD133(+) cells from tumor tissue, offering a key tool for research in tumor biology and cancer therapy.
...

45 References

Interferon resistance of cutaneous T-cell lymphoma-derived clonal T-helper 2 cells allows selective viral replication.

The IFN resistance of the dominant T-helper 2 cells might be important for lymphomagenesis and interferon signaling deficiencies can be targeted for purging patients' cells in vitro, resulting in the efficient treatment of CTCL and other IFN-resistant neoplasms such as lung cancer.

An oncolytic measles virus engineered to enter cells through the CD20 antigen.

Systemic therapy of myeloma xenografts by an attenuated measles virus.

It is shown that the live attenuated Edmonston-B vaccine strain of measles virus (MV-Edm) replicates selectively in human myeloma cells and has potent antitumor activity.

Oncolytic measles viruses displaying a single-chain antibody against CD38, a myeloma cell marker.

A new specificity domain against the plasma cell marker CD38 was constructed in the form of a single-chain antibody (scFv) and display of that scFv on the measles viral envelope glycoprotein successfully redirected virus entry through CD38 expressed on target cells devoid of the natural MV receptors.

Live attenuated measles virus induces regression of human lymphoma xenografts in immunodeficient mice.

The vaccine strain of MV mediates regression of large, established human B-cell lymphoma xenografts in SCID mice, and proof of principle is established that MV is oncolytic for lymphomas in vivo, indicating its value as a novel replicating-virus therapy for this group of disorders.

Exploiting tumor-specific defects in the interferon pathway with a previously unknown oncolytic virus

Vesicular stomatitis virus (VSV), an enveloped, negative-sense RNA virus exquisitely sensitive to treatment with interferon, is used as a replication-competent oncolytic virus and a new strategy for the treatment of interferons non-responsive tumors is demonstrated.

Interferon-alpha resistance in a cutaneous T-cell lymphoma cell line is associated with lack of STAT1 expression.

The development of an IFN alpha-resistant CTCL cell line (HUT78R), characterized by its ability to proliferate in high concentration of recombinant IFNalpha, which can be used as a model system to study IFN resistance.

The interferon inhibiting cytokine IK is overexpressed in cutaneous T cell lymphoma derived tumor cells that fail to upregulate major histocompatibility complex class II upon interferon-gamma stimulation.

It is suggested that interferon inhibiting cytokine factor contributes to the lack of HLA class II upregulation in lymphoma cells, and may participate in providing a microenvironment at the tumor site insensitive tointerferon-gamma stimulation and thus prevents an efficient local immune response.

Biodistribution of oncolytic measles virus after intraperitoneal administration into Ifnar-CD46Ge transgenic mice.

It is suggested that, after intraperitoneal virus administration, the positive cells in thoracic lymphatics, parathymic lymph nodes, and spleen are nonmigratory cells transduced in situ by viral particles that have exited from the peritoneal cavity.

Sézary syndrome T-cell clones display T-helper 2 cytokines and express the accessory factor-1 (interferon-gamma receptor beta-chain).

The T-helper 2 cytokine spectrum of all clones investigated is associated with overexpression of AF-1, which weakens cell-mediated immunosurveillance, and explains the clinical and immunologic abnormalities in SS patients.