scholarly journals Inhibition of Indoleamine-2,3-dioxygenase (IDO) in Glioblastoma Cells by Oncolytic Herpes Simplex Virus

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Bonnie Reinhart ◽  
Lucia Mazzacurati ◽  
Adriana Forero ◽  
Chang-Sook Hong ◽  
Junichi Eguchi ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Virus Replication ◽  
Immune Escape ◽  
Immune Surveillance ◽  
Innate Immune ◽  
Glioblastoma Cells ◽  
Indoleamine 2,3 Dioxygenase ◽  
Oncolytic Herpes Simplex Virus ◽  
Hel Cells ◽  
Simplex Virus

Successful oncolytic virus treatment of malignant glioblastoma multiforme depends on widespread tumor-specific lytic virus replication and escape from mitigating innate immune responses to infection. Here we characterize a new HSV vector, JD0G, that is deleted for ICP0 and the joint sequences separating the unique long and short elements of the viral genome. We observed that JD0G replication was enhanced in certain glioblastoma cell lines compared to HEL cells, suggesting that a vector backbone deleted for ICP0 may be useful for treatment of glioblastoma. The innate immune response to virus infection can potentially impede oncolytic vector replication in human tumors. Indoleamine-2,3-dioxygenase (IDO) is expressed in response to interferonγ(IFNγ) and has been linked to both antiviral functions and to the immune escape of tumor cells. We observed that IFNγtreatment of human glioblastoma cells induced the expression of IDO and that this expression was quelled by infection with both wild-type and JD0G viruses. The role of IDO in inhibiting virus replication and the connection of this protein to the escape of tumor cells from immune surveillance suggest that IDO downregulation by HSV infection may enhance the oncolytic activity of vectors such as JD0G.

scholarly journals An oncolytic virus expressing a full-length antibody enhances antitumor innate immune response to glioblastoma

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Bo Xu ◽  
Lei Tian ◽  
Jing Chen ◽  
Jing Wang ◽  
Rui Ma ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Nk Cells ◽  
Herpes Virus ◽  
Innate Immune ◽  
Full Length ◽  
Herpes Simplex Virus 1 ◽  
Oncolytic Herpes Simplex Virus ◽  
Herpès Virus ◽  
Simplex Virus

AbstractOncolytic herpes simplex virus-1 is capable of lysing tumor cells while alerting the immune system. CD47, in collaboration with SIRPα, represents an important immune checkpoint to inhibit phagocytosis by innate immune cells. Here we show locoregional control of glioblastoma by an oncolytic herpes virus expressing a full-length anti(α)-human CD47 IgG1 or IgG4 antibody. The antibodies secreted by the virus-infected glioblastoma cells block the CD47 ‘don’t eat me’ signal irrespective of the subclass; however, αCD47-IgG1 has a stronger tumor killing effect than αCD47-IgG4 due to additional antibody-dependent cellular phagocytosis by macrophages and antibody-dependent cellular cytotoxicity by NK cells. Intracranially injected αCD47-IgG1-producing virus continuously releases the respective antibody in the tumor microenvironment but not into systemic circulation; additionally, αCD47-IgG1-producing virus also improves the survival of tumor-bearing mice better than control oncolytic herpes virus combined with topical αCD47-IgG1. Results from immunocompetent mouse tumor models further confirm that macrophages, and to a lesser extent NK cells, mediate the anti-tumor cytotoxicity of antibody-producing oncolytic herpesviruses. Collectively, oncolytic herpes simplex virus-1 encoding full-length antibodies could improve immune-virotherapy for glioblastoma.

Effect of a third-generation oncolytic herpes simplex virus on the growth of human hepatocellular carcinoma.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 321-321
Author(s):  
Richi Nakatake ◽  
Masaki Kaibori ◽  
Yusuke Nakamura ◽  
Hideyuki Matsushima ◽  
Tadayoshi Okumura ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Herpes Simplex ◽  
Immune Responses ◽  
Tumor Cells ◽  
Cell Lines ◽  
Third Generation ◽  
Oncolytic Herpes Simplex Virus ◽  
Xenograft Models ◽  
Simplex Virus

321 Background: Multimodality therapies are used to manage patients with hepatocellular carcinoma (HCC), although advanced HCC is incurable. The third-generation oncolytic herpes simplex virus type 1 (HSV-1) T-01 replicates efficiently and selectively in tumor cells, kills tumor cells without damaging the surrounding normal tissues, and induces host immune responses specific to tumor cells. Here we investigated the antitumor effects of T-01 on HCC. Methods: The cytopathic activities of T-01 were tested at different multiplicities of infection in 14 human and one murine hepatoma cell lines in vitro. In mouse various xenograft models, HuH-7, KYN-2, PLC/PRF/5 and HepG2 human cells and Hepa1-6 murine cells were used to investigate the in vivo efficacy of T-01. Results: T-01 was cytotoxic to 13 cell lines (in vitro), including 10 human HCCs, two human hepatoblastomas, and one murine hepatoma. In mouse xenograft models of subcutaneous, orthotopic, and peritoneal tumor metastasis in athymic mice (BALB/c nu/nu), the growth of tumors formed by the HCC cell lines HuH-7, KYN-2, and PLC/PRF/5 as well as those formed by the hepatoblastoma cell line HepG2 was inhibited by T-01 compared with that of mock-inoculated tumors. In a bilateral Hepa1-6 subcutaneous tumor model in C57BL/6 mice, the growth of tumors inoculated with T-01 was inhibited and, in the contralateral tumors without T-01, T-01 also significantly reduced tumor growth compared with mock-infected tumors. T-01 infection significantly enhanced antitumor efficacy via T cell-mediated immune responses. Conclusions: These results demonstrate that a third-generation oncolytic HSV-1 may serve as a novel treatment for patients with HCC.

scholarly journals Role of Indoleamine-2,3-Dioxygenase in Alpha/Beta and Gamma Interferon-Mediated Antiviral Effects against Herpes Simplex Virus Infections

2004 ◽  
Vol 78 (5) ◽  
pp. 2632-2636 ◽  
Author(s):  
O. Adams ◽  
K. Besken ◽  
C. Oberdörfer ◽  
C. R. MacKenzie ◽  
O. Takikawa ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Replication ◽  
Cell Types ◽  
Antiviral Effect ◽  
Gamma Interferon ◽  
Virus Infections ◽  
Indoleamine 2,3 Dioxygenase ◽  
Ifn Γ ◽  
Simplex Virus

ABSTRACT Gamma interferon (IFN-γ)-mediated indoleamine-2,3-dioxygenase (IDO) activity in human astrocytoma cells and in native astrocytes was found to be responsible for the inhibition of herpes simplex virus replication. The effect is abolished in the presence of excess amounts of l-tryptophan. Both IFN-α and IFN-β restricted herpes simplex virus replication in both cell types, but (in contrast to the results seen with IFN-γ) the addition of an excess amount of l-tryptophan did not inhibit the induced antiviral effect.

scholarly journals Hematological Malignancies Escape from NK Cell Innate Immune Surveillance: Mechanisms and Therapeutic Implications

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Laure Farnault ◽  
Carole Sanchez ◽  
Céline Baier ◽  
Thérèse Le Treut ◽  
Régis T. Costello
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Tumor Cells ◽  
Immune Modulation ◽  
Hematological Malignancies ◽  
Nk Cell ◽  
Immune Surveillance ◽  
Innate Immune ◽  
Allogenic Stem Cell Transplantation ◽  
Therapeutic Implications

Hematological malignancies treatment improved over the last years resulting in increased achievement of complete or partial remission, but unfortunately high relapse rates are still observed. Therefore, sustainment of long-term remission is crucial. Immune system has a key role in tumor surveillance. Natural killer (NK) cells, at the frontier of innate and adaptive immune system, have a central role in tumor cells surveillance as demonstrated in the setting of allogenic stem cell transplantation. Nevertheless, tumor cells develop various mechanisms to escape from NK cells innate immune pressure. Abnormal NK cytolytic functions have been described in nearly all hematological malignancies. We present here various mechanisms involved in the escape of hematological malignancies from NK cells surveillance: NK cells quantitative deficiency and NK cell qualitative deficiency by increased inhibition signaling or decreased activating stimuli. A challenge of immunotherapy is to restore an efficient antitumor response. A combination of classical therapy plus immune modulation strategies will soon become a standard of care for hematological malignancies.

scholarly journals Replication and Spread of Oncolytic Herpes Simplex Virus in Solid Tumors

Viruses ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 118
Author(s):  
Bangxing Hong ◽  
Upasana Sahu ◽  
Matthew P. Mullarkey ◽  
Balveen Kaur
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Stromal Cells ◽  
Tumor Antigens ◽  
Oncolytic Herpes Simplex Virus ◽  
Promising Treatment ◽  
Simplex Virus ◽  
Insight Into

Oncolytic herpes simplex virus (oHSV) is a highly promising treatment for solid tumors. Intense research and development efforts have led to first-in-class approval for an oHSV for melanoma, but barriers to this promising therapy still exist that limit efficacy. The process of infection, replication and transmission of oHSV in solid tumors is key to obtaining a good lytic destruction of infected cancer cells to kill tumor cells and release tumor antigens that can prime anti-tumor efficacy. Intracellular tumor cell signaling and tumor stromal cells present multiple barriers that resist oHSV activity. Here, we provide a review focused on oncolytic HSV and the essential viral genes that allow for virus replication and spread in order to gain insight into how manipulation of these pathways can be exploited to potentiate oHSV infection and replication among tumor cells.

scholarly journals Metastatic Colonization: Escaping Immune Surveillance

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3385 ◽  
Author(s):  
Julien Schaller ◽  
Judith Agudo
Keyword(s):  
Immune Responses ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Immune Escape ◽  
Current Knowledge ◽  
Immune Surveillance ◽  
New Host ◽  
Primary Tumors ◽  
Metastatic Colonization ◽  
Tumor Dissemination

Cancer immunotherapy has shifted the paradigm in cancer therapy by revitalizing immune responses against tumor cells. Specifically, in primary tumors cancer cells evolve in an immunosuppressive microenvironment, which protects them from immune attack. However, during tumor progression, some cancer cells leave the protective tumor mass, disseminating and seeding secondary organs. These initial disseminated tumor cells (DTCs) should potentially be susceptible to recognition by the immune system in the new host tissues. Although Natural Killer or T cells eliminate some of these DTCs, a fraction escape anti-tumor immunity and survive, thus giving rise to metastatic colonization. How DTCs interact with immune cells and the underpinnings that regulate imperfect immune responses during tumor dissemination remain poorly understood. Uncovering such mechanisms of immune evasion may contribute to the development of immunotherapy specifically targeting DTCs. Here we review current knowledge about systemic and site-specific immune-cancer crosstalk in the early steps of metastasis formation. Moreover, we highlight how conventional cancer therapies can shape the pre-metastatic niche enabling immune escape of newly arrived DTCs.

scholarly journals Extracellular Vesicles Released by Herpes Simplex Virus 1-Infected Cells Block Virus Replication in Recipient Cells in a STING-Dependent Manner

2018 ◽  
Vol 92 (18) ◽  
Author(s):  
Thibaut Deschamps ◽  
Maria Kalamvoki
Keyword(s):  
Extracellular Vesicles ◽  
Virus Replication ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Herpes Simplex Virus 1 ◽  
Density Fractions ◽  
Infected Cells ◽  
Simplex Virus ◽  
M1 Type ◽  
Hsv 1

ABSTRACT Herpes simplex virus 1 (HSV-1)-infected cells release extracellular vesicles (EVs) that deliver to uninfected cells viral factors and host components, such as the stimulator of interferon genes (STING), which activates type I interferon upon foreign DNA sensing. The functions of EVs released by HSV-1-infected cells have remained unknown. Here, we describe a procedure to separate the EVs from HSV-1 virions that is based on an iodixanol/sucrose gradient. STING, along with the EV markers CD63 and CD9, was found in light-density fractions, while HSV components accumulated in heavy-density fractions. HSV-1 infection stimulated the release of EVs from the cells. The EVs derived from infected cells, but not from uninfected cells, activated innate immunity in recipient cells and suppressed viral gene expression and virus replication. Moreover, only the EVs derived from infected cells stimulated the expression of a subset of M1-type markers in recipient macrophages. Conversely, EVs derived from STING-knockdown cells failed to stimulate the expression of these M1-type markers, they activated innate immune responses to a lesser extent in recipient cells, and they did not sustain the inhibition of virus replication. These data suggest that STING from the EV donor cells contributes to the antiviral responses in cells receiving EVs from HSV-1-infected cells. Perturbations in the biogenesis of EVs by silencing CD63 or blocking the activity of the neutral spingomyelinase-2 (nSMase-2) increased the HSV-1 yields. Overall, our data suggest that the EVs released from HSV-1-infected cells negatively impact the infection and could control the dissemination of the virus. IMPORTANCE Extracellular vesicles (EVs) are released by all types of cells as they constitute major mechanism of intercellular communication and have the capacity to alter the functions of recipient cells despite their limited capacity for cargo. How the EVs released by HSV-infected cells could alter the surrounding microenvironment and influence the infection currently remains unknown. The cargo of EVs reflects the physiological state of the cells in which they were produced, so the content of EVs originating from infected cells is expected to be substantially different from that of healthy cells. Our studies indicate that the EVs released by HSV-1-infected cells carry innate immune components such as STING and other host and viral factors; they can activate innate immune responses in recipient cells and inhibit HSV-1 replication. The implication of these data is that the EVs released by HSV-1-infected cells could control HSV-1 dissemination promoting its persistence in the host.

Sign in / Sign up

Export Citation Format

Share Document