Oncolytic polio virotherapy of cancer. 2014

Michael C Brown, and Elena Y Dobrikova, and Mikhail I Dobrikov, and Ross W Walton, and Sarah L Gemberling, and Smita K Nair, and Annick Desjardins, and John H Sampson, and Henry S Friedman, and Allan H Friedman, and Douglas S Tyler, and Darell D Bigner, and Matthias Gromeier
Department of Surgery, Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina; Division of Neurosurgery Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina; Department of Molecular Genetics and Microbiology, Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina.

Recently, the century-old idea of targeting cancer with viruses (oncolytic viruses) has come of age, and promise has been documented in early stage and several late-stage clinical trials in a variety of cancers. Although originally prized for their direct tumor cytotoxicity (oncolytic virotherapy), recently, the proinflammatory and immunogenic effects of viral tumor infection (oncolytic immunotherapy) have come into focus. Indeed, a capacity for eliciting broad, sustained antineoplastic effects stemming from combined direct viral cytotoxicity, innate antiviral activation, stromal proinflammatory stimulation, and recruitment of adaptive immune effector responses is the greatest asset of oncolytic viruses. However, it also is the source for enormous mechanistic complexity that must be considered for successful clinical translation. Because of fundamentally different relationships with their hosts (malignant or not), diverse replication strategies, and distinct modes of tumor cytotoxicity/killing, oncolytic viruses should not be referred to collectively. These agents must be evaluated based on their individual merits. In this review, the authors highlight key mechanistic principles of cancer treatment with the polio:rhinovirus chimera PVSRIPO and their implications for oncolytic immunotherapy in the clinic.

UI MeSH Term Description Entries
D007113 Immunity, Innate The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS. Immunity, Native,Immunity, Natural,Immunity, Non-Specific,Resistance, Natural,Innate Immune Response,Innate Immunity,Immune Response, Innate,Immune Responses, Innate,Immunity, Non Specific,Innate Immune Responses,Native Immunity,Natural Immunity,Natural Resistance,Non-Specific Immunity
D007167 Immunotherapy Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. Immunotherapies
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D011051 Poliomyelitis An acute infectious disease of humans, particularly children, caused by any of three serotypes of human poliovirus (POLIOVIRUS). Usually the infection is limited to the gastrointestinal tract and nasopharynx, and is often asymptomatic. The central nervous system, primarily the spinal cord, may be affected, leading to rapidly progressive paralysis, coarse FASCICULATION and hyporeflexia. Motor neurons are primarily affected. Encephalitis may also occur. The virus replicates in the nervous system, and may cause significant neuronal loss, most notably in the spinal cord. A rare related condition, nonpoliovirus poliomyelitis, may result from infections with nonpoliovirus enteroviruses. (From Adams et al., Principles of Neurology, 6th ed, pp764-5) Infantile Paralysis,Polio,Poliomyelitis, Nonpoliovirus,Poliomyelitis, Preparalytic,Encephalitis, Polio,Epidemic Acute Poliomyelitis,Polio Encephalitis,Poliomyelitis Infection,Poliomyelitis, Acute,Acute Poliomyelitis,Acute Poliomyelitis, Epidemic,Infection, Poliomyelitis,Infections, Poliomyelitis,Nonpoliovirus Poliomyelitis,Paralysis, Infantile,Poliomyelitides, Preparalytic,Poliomyelitis Infections,Poliomyelitis, Epidemic Acute,Polios,Preparalytic Poliomyelitis
D011991 Receptors, Virus Specific molecular components of the cell capable of recognizing and interacting with a virus, and which, after binding it, are capable of generating some signal that initiates the chain of events leading to the biological response. Viral Entry Receptor,Viral Entry Receptors,Virus Attachment Factor,Virus Attachment Factors,Virus Attachment Receptor,Virus Attachment Receptors,Virus Entry Receptor,Virus Entry Receptors,Virus Receptor,Virus Receptors,Attachment Factor, Virus,Attachment Factors, Virus,Attachment Receptor, Virus,Attachment Receptors, Virus,Entry Receptor, Viral,Entry Receptor, Virus,Entry Receptors, Viral,Entry Receptors, Virus,Receptor, Viral Entry,Receptor, Virus,Receptor, Virus Attachment,Receptor, Virus Entry,Receptors, Viral Entry,Receptors, Virus Attachment,Receptors, Virus Entry
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D050130 Oncolytic Virotherapy Use of attenuated VIRUSES as ANTINEOPLASTIC AGENTS to selectively kill CANCER cells. Oncolytic Virus Therapy,Virotherapy, Oncolytic,Oncolytic Virotherapies,Oncolytic Virus Therapies,Therapies, Oncolytic Virus,Therapy, Oncolytic Virus,Virotherapies, Oncolytic,Virus Therapies, Oncolytic,Virus Therapy, Oncolytic
D050504 Oncolytic Viruses Tumor-selective, replication competent VIRUSES that have antineoplastic effects. This is achieved by producing cytotoxicity-enhancing proteins and/or eliciting an antitumor immune response. They are genetically engineered so that they can replicate in CANCER cells but not in normal cells, and are used in ONCOLYTIC VIROTHERAPY. Oncolytic Virus,Virus, Oncolytic,Viruses, Oncolytic
D053586 Virus Internalization The entering of cells by viruses following VIRUS ATTACHMENT. This is achieved by ENDOCYTOSIS, by translocation of the whole virus across the cell membrane, by direct MEMBRANE FUSION of the viral membrane with the CELL MEMBRANE, or by fusion of the membrane of infected cells with the membrane of non-infected cells causing SYNCYTIA to be formed. Viral Entry,Viral Internalization,Viral Membrane Fusion,Virus Entry,Virus Membrane Fusion,Entry, Viral,Entry, Virus,Fusion, Viral Membrane,Internalization, Viral,Internalization, Virus,Membrane Fusion, Viral

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