Effects of innate immunity on herpes simplex virus and its ability to kill tumor cells.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 9421525 Publication Model: Print Cited Medium: Print ISSN: 0969-7128 (Print) Linking ISSN: 09697128 NLM ISO Abbreviation: Gene Ther Subsets: MEDLINE

Publication: London : Nature Publishing Group
Original Publication: Houndmills, Basingstoke, Hampshire, UK : Macmillan Press Ltd., c1994-

Genetic Therapy/*methods ; Genetic Vectors/*immunology ; Herpes Simplex/*immunology ; Herpesvirus 1, Human/*immunology ; Neoplasms/*therapy ; Viruses/*immunology; Animals ; Brain Neoplasms/immunology ; Brain Neoplasms/therapy ; Brain Neoplasms/virology ; Central Nervous System/immunology ; Central Nervous System/virology ; Complement Inactivator Proteins/therapeutic use ; Complement System Proteins/immunology ; Cyclophosphamide/therapeutic use ; Herpes Simplex/complications ; Humans ; Immunosuppressive Agents/therapeutic use ; Neoplasms/immunology ; Neoplasms/virology ; Virus Replication

Several clinical trials have or are being performed testing the safety and efficacy of different strains of oncolytic viruses (OV) for malignant cancers. OVs represent either naturally occurring or genetically engineered strains of viruses that exhibit relatively selective replication in tumor cells. Several types of OV have been derived from herpes simplex virus 1 (HSV1). Tumor oncolysis depends on the processes of initial OV infection of tumor, followed by subsequent propagation of OV within the tumor itself. The role of the immune responses in these processes has not been extensively studied. On the contrary, effects of the immune response on the processes of wild-type HSV1 infection and propagation in the central nervous system have been studied and described in detail. The first line of defense against a wild-type HSV1 infection in both naive and immunized individuals is provided by innate humoral (complement, cytokines, chemokines) and cellular (macrophages, neutrophils, NK cells, gammadelta T cells, and interferon-producing cells) responses. These orchestrate the lysis of virions and virus-infected cells as well as provide a link to effective adaptive immunity. The role of innate defenses in curtailing the oncolytic effect of genetically engineered HSV has only recently been studied, but several of the same host responses appear to be operative in limiting anticancer effects by the replicating virus. The importance of this knowledge lies in finding avenues to modulate such initial innate responses, in order to allow for increased oncolysis of tumors while minimizing host toxicity.

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0 (Complement Inactivator Proteins)
0 (Immunosuppressive Agents)
8N3DW7272P (Cyclophosphamide)
9007-36-7 (Complement System Proteins)

Date Created: 20030521 Date Completed: 20030623 Latest Revision: 20220914

20240829

10.1038/sj.gt.3302038

12756419