Mechanisms of measles virus oncolytic immunotherapy

Measles virus (MeV) preferentially replicates in malignant cells, leading to tumor lysis and priming of antitumor immunity. Live attenuated MeV vaccine strains are therefore under investigation as cancer therapeutics. The versatile MeV reverse genetics systems allows for engineering of advanced targeted, armed, and shielded oncolytic viral vectors. Therapeutic efficacy can further be enhanced by combination treatments. An emerging focus in this regard is combination immunotherapy, especially with immune checkpoint blockade. Despite challenges arising from antiviral immunity, availability of preclinical models, and GMP production, early clinical trials have demonstrated safety of oncolytic MeV and yielded promising efficacy data. Future clinical trials with engineered viruses, rational combination regimens, and comprehensive translational research programs will realize the potential of oncolytic immunotherapy.

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Use of Protein a Conjugated to Peroxidase to Localize Immunoglobulin G in SSPE Ferret Brain

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100054376 ◽

1982 ◽

Vol 40 ◽

pp. 350-351

Author(s):

Hannah R. Brown ◽

Anthony F. Nostro ◽

Halldor Thormar

Keyword(s):

Immunoglobulin G ◽

Human Disease ◽

Measles Virus ◽

Subacute Sclerosing Panencephalitis ◽

Protein A ◽

Inflammatory Lesions ◽

Sspe Virus ◽

Specific Immunoglobulin ◽

Antibody Titers ◽

The Brain

Subacute sclerosing panencephalitis (SSPE) is a slowly progressing disease of the CNS in children which is caused by measles virus. Ferrets immunized with measles virus prior to inoculation with the cell associated, syncytiogenic D.R. strain of SSPE virus exhibit characteristics very similar to the human disease. Measles virus nucleocapsids are present, high measles antibody titers are found in the sera and inflammatory lesions are prominent in the brains. Measles virus specific immunoglobulin G (IgG) is present in the brain,and IgG/ albumin ratios indicate that the antibodies are synthesized within the CNS.

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Presence of antibody in virus-infected brain cells of SSPE ferrets

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100077591 ◽

1983 ◽

Vol 41 ◽

pp. 804-805

Author(s):

Hannah R. Brown ◽

Tammy L. Donato ◽

Halldor Thormar

Keyword(s):

Measles Virus ◽

Plasma Cells ◽

Subacute Sclerosing Panencephalitis ◽

Protein A ◽

Neutralizing Antibody ◽

Brain Cells ◽

Antibody Titers ◽

A Cell ◽

The Central Nervous System ◽

The Brain

Measles virus specific immunoglobulin G (IgG) has been found in the brains of patients with subacute sclerosing panencephalitis (SSPE), a slowly progressing disease of the central nervous system (CNS) in children. IgG/albumin ratios indicate that the antibodies are synthesized within the CNS. Using the ferret as an animal model to study the disease, we have been attempting to localize the Ig's in the brains of animals inoculated with a cell associated strain of SSPE. In an earlier report, preliminary results using Protein A conjugated to horseradish peroxidase (PrAPx) (Dynatech Diagnostics Inc., South Windham, ME.) to detect antibodies revealed the presence of immunoglobulin mainly in antibody-producing plasma cells in inflammatory lesions and not in infected brain cells.In the present experiment we studied the brain of an SSPE ferret with neutralizing antibody titers of 1:1024 in serum and 1:512 in CSF at time of sacrifice 7 months after i.c. inoculation with SSPE measles virus-infected cells. The animal was perfused with saline and portions of the brain and spinal cord were immersed in periodate-lysine-paraformaldehyde (P-L-P) fixative. The ferret was not perfused with fixative because parts of the brain were used for virus isolation.

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Studies of a Defective Measles Virus

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100100780 ◽

1968 ◽

Vol 26 ◽

pp. 208-209

Author(s):

R. M. McCombs ◽

M. Benyesh-Melnick ◽

J. P. Brunschwig

Keyword(s):

Inclusion Bodies ◽

Measles Virus ◽

Giant Cells ◽

Helical Structures ◽

Thin Sections ◽

Virus Particles ◽

Extracellular Virus ◽

Culture Cells ◽

Infected Cells ◽

Eosinophilic Inclusions

Measles virus is an agent that is capable of replicating in a number of different culture cells and generally causes the formation of multinucleated giant cells. As a result of infection, virus is released from the cells into the culture fluids and reinfection can be initiated by this cell-free virus. The extracellular virus has been examined by negative staining with phosphotungstic acid and has been shown to be a rather pleomorphic particle with a diameter of about 140 mμ. However, no such virus particles have been detected in thin sections of the infected cells. Rather, the only virus-induced structures present in the giant cells are eosinophilic inclusions (intracytoplasmic or intranuclear). These inclusion bodies have been shown to contain helical structures, resembling the nucleocapsid observed in negatively stained preparations.

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