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Oncolytic HSV and T cells

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https://www.readbyqxmd.com/read/28507788/adaptive-t-cell-responses-induced-by-oncolytic-herpes-simplex-virus-granulocyte-macrophage-colony-stimulating-factor-therapy-expanded-by-dendritic-cell-and-cytokine-induced-killer-cell-adoptive-therapy
#1
Jun Ren, William R Gwin, Xinna Zhou, Xiaoli Wang, Hongyan Huang, Ni Jiang, Lei Zhou, Pankaj Agarwal, Amy Hobeika, Erika Crosby, Zachary C Hartman, Michael A Morse, Kevin H Eng, H Kim Lyerly
Purpose: Although local oncolytic viral therapy (OVT) may enhance tumor lysis, antigen release, and adaptive immune responses, systemic antitumor responses post-therapy are limited. Adoptive immunotherapy with autologous dendritic cells (DC) and cytokine-induced killer cells (DC-CIK) synergizes with systemic therapies. We hypothesized that OVT with Herpes Simplex Virus-granulocyte macrophage-colony-stimulating factor (HSV-GM-CSF) would induce adaptive T cell responses that could be expanded systemically with sequential DC-CIK therapy...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28331843/curative-effect-of-hf10-on-liver-and-peritoneal-metastasis-mediated-by-host-antitumor-immunity
#2
Yoshihiro Hotta, Hideki Kasuya, Itzel Bustos, Yoshinori Naoe, Toru Ichinose, Maki Tanaka, Yasuhiro Kodera
BACKGROUND: HF10 is a highly attenuated type 1 herpes simplex virus (HSV) with proven effective oncolytic effect. Previous investigations have demonstrated that colon cancer mice model treated with HF10 not only had better survival but were also resistant to the reimplantation of the antitumor effect mediated by host antitumor immunity. Importantly, it has also been noted that in mice with antitumors implanted on both sides of the back, an injection of HF10 on only one side strongly restrains not only the injected antitumor but also the non-injected ones...
2017: Oncolytic Virotherapy
https://www.readbyqxmd.com/read/28319448/rationale-and-design-of-a-phase-1-clinical-trial-to-evaluate-hsv-g207-alone-or-with-a-single-radiation-dose-in-children-with-progressive-or-recurrent-malignant-supratentorial-brain-tumors
#3
Alicia M Waters, James M Johnston, Alyssa T Reddy, John Fiveash, Avi Madan-Swain, Kara Kachurak, Asim K Bag, G Yancey Gillespie, James M Markert, Gregory K Friedman
Primary central nervous system tumors are the most common solid neoplasm of childhood and the leading cause of cancer-related death in pediatric patients. Survival rates for children with malignant supratentorial brain tumors are poor despite aggressive treatment with combinations of surgery, radiation, and chemotherapy, and survivors often suffer from damaging lifelong sequelae from current therapies. Novel innovative treatments are greatly needed. One promising new approach is the use of a genetically engineered, conditionally replicating herpes simplex virus (HSV) that has shown tumor-specific tropism and potential efficacy in the treatment of malignant brain tumors...
March 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28253733/rationale-and-design-of-a-phase-i-clinical-trial-to-evaluate-hsv-g207-alone-or-with-a-single-radiation-dose-in-children-with-progressive-or-recurrent-malignant-supratentorial-brain-tumors
#4
Alicia M Waters, James M Johnston, Alyssa T Reddy, John Fiveash, Avi Madan-Swain, Kara Kachurak, Asim K Bag, G Yancey Gillespie, James M Markert, Gregory K Friedman
Primary central nervous system tumors are the most common solid neoplasm of childhood and the leading cause of cancer related death in pediatric patients. Survival rates for children with malignant supratentorial brain tumors are poor despite aggressive treatment with combinations of surgery, radiation, and chemotherapy; and survivors often suffer from damaging lifelong sequelae from current therapies. Novel innovative treatments are greatly needed. One promising new approach is the use of a genetically engineered, conditionally replicating herpes simplex virus (HSV) that has shown tumor specific tropism and potential efficacy in the treatment of malignant brain tumors...
February 24, 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/28074746/oncology-s-trojan-horse-using-viruses-to-battle-cancer
#5
REVIEW
Heena J Mavani, Jeannette Y Wick
In 2016, the American health care system was faced with more than 1.6 million new cases of cancer, and individuals older than 65 years of age will be affected disproportionately. Many older individuals are poor candidates for traditional treatments (e.g., chemotherapy, radiation) because of actual or potential treatment-related adverse events. Researchers continuously look for novel therapeutic strategies, and an exciting new one is on the horizon: virotherapy. Viruses' ability to infect and kill human cells makes them promising cancer treatments...
December 1, 2016: Consultant Pharmacist: the Journal of the American Society of Consultant Pharmacists
https://www.readbyqxmd.com/read/28061981/talimogene-laherparepvec-t-vec-for-the-treatment-of-melanoma-and-other-cancers
#6
REVIEW
Claud Grigg, Zoë Blake, Robyn Gartrell, Adrian Sacher, Bret Taback, Yvonne Saenger
Talimogene laherparepvec (T-Vec) is the first live virus to be approved by the US Food and Drug Administration for the treatment of cancer. This engineered version of herpes simplex virus type 1 (HSV-1) is the product of decades of preclinical work aimed at identifying and modifying aspects of the viral genome involved in virulence and immunogenicity. T-Vec preferentially infects and lyses tumor cells and, in some cases, induces a systemic immune response against the tumor. These properties have translated into significant and durable clinical responses, particularly in advanced melanoma...
December 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/27610392/effect-of-hsv-il12-loaded-tumor-cell-based-vaccination-in-a-mouse-model-of-high-grade-neuroblastoma
#7
David F Bauer, Larisa Pereboeva, G Yancey Gillespie, Gretchen A Cloud, Osama Elzafarany, Catherine Langford, James M Markert, Lawrence S Lamb
We designed multimodal tumor vaccine that consists of irradiated tumor cells infected with the oncolytic IL-12-expressing HSV-1 virus, M002. This vaccine was tested against the syngeneic neuroblastoma mouse model Neuro 2a injected into the right caudate nucleus of the immunocompetent A/J mice. Mice were vaccinated via intramuscular injection of multimodal vaccine or uninfected irradiated tumor cells at seven and 14 days after tumor establishment. While there was no survival difference between groups vaccinated with cell-based vaccine applied following tumor injection, a premunition prime/boost vaccination strategy produced a significant survival advantage in both groups and sustained immune response to an intracranial rechallenge of the same tumor...
2016: Journal of Immunology Research
https://www.readbyqxmd.com/read/27486853/oncolytic-virus-therapy-a-new-era-of-cancer-treatment-at-dawn
#8
REVIEW
Hiroshi Fukuhara, Yasushi Ino, Tomoki Todo
Oncolytic virus therapy is perhaps the next major breakthrough in cancer treatment following the success in immunotherapy using immune checkpoint inhibitors. Oncolytic viruses are defined as genetically engineered or naturally occurring viruses that selectively replicate in and kill cancer cells without harming the normal tissues. T-Vec (talimogene laherparepvec), a second-generation oncolytic herpes simplex virus type 1 (HSV-1) armed with GM-CSF, was recently approved as the first oncolytic virus drug in the USA and Europe...
October 2016: Cancer Science
https://www.readbyqxmd.com/read/27390350/bortezomib-treatment-sensitizes-oncolytic-hsv-1-treated-tumors-to-nk-cell-immunotherapy
#9
Ji Young Yoo, Alena Cristina Jaime-Ramirez, Chelsea Bolyard, Hongsheng Dai, Tejaswini Nallanagulagari, Jeffrey Wojton, Brian S Hurwitz, Theresa Relation, Tae Jin Lee, Michael T Lotze, Jun-Ge Yu, Jianying Zhang, Carlo M Croce, Jianhua Yu, Michael A Caligiuri, Matthew Old, Balveen Kaur
PURPOSE: Both the proteasome inhibitor bortezomib and an oncolytic herpes simplex virus-1 (oHSV)-expressing GM-CSF are currently FDA approved. Although proteasome blockade can increase oHSV replication, immunologic consequences, and consequent immunotherapy potential are unknown. In this study, we investigated the impact of bortezomib combined with oHSV on tumor cell death and sensitivity to natural killer (NK) cell immunotherapy. EXPERIMENTAL DESIGN: Western blot, flow cytometry, and caspase 3/7 activity assays were used to evaluate the induction of apoptosis/autophagy and/or necroptotic cell death...
November 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27077112/cd8-t-cell-immune-evasion-enables-oncolytic-virus-immunotherapy
#10
Aldo Pourchet, Steven R Fuhrmann, Karsten A Pilones, Sandra Demaria, Alan B Frey, Matthew Mulvey, Ian Mohr
Although counteracting innate defenses allows oncolytic viruses (OVs) to better replicate and spread within tumors, CD8(+) T-cells restrict their capacity to trigger systemic anti-tumor immune responses. Herpes simplex virus-1 (HSV-1) evades CD8(+) T-cells by producing ICP47, which limits immune recognition of infected cells by inhibiting the transporter associated with antigen processing (TAP). Surprisingly, removing ICP47 was assumed to benefit OV immuno-therapy, but the impact of inhibiting TAP remains unknown because human HSV-1 ICP47 is not effective in rodents...
March 2016: EBioMedicine
https://www.readbyqxmd.com/read/26987291/immunogenic-cell-death-by-oncolytic-herpes-simplex-virus-type-1-in-squamous-cell-carcinoma-cells
#11
A Takasu, A Masui, M Hamada, T Imai, S Iwai, Y Yura
Molecules essential for the induction of immunogenic cell death (ICD) are called damage-associated molecular patterns (DAMPs). The effects of oncolytic herpes simplex virus type 1 (HSV-1) on the production of DAMPs were examined in squamous cell carcinoma (SCC) cells. The cytopathic effects of HSV-1 RH2 were observed in mouse SCCVII cells infected at a high multiplicity of infection (MOI), and the amounts of viable cells were decreased. After being infected with RH2, ATP and high mobility group box 1 (HMGB1) were released extracellulary, while calreticulin (CRT) translocated to the cell membrane...
April 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/26941401/uv-inactivated-hsv-1-potently-activates-nk-cell-killing-of-leukemic-cells
#12
Ismael Samudio, Katayoun Rezvani, Hila Shaim, Elyse Hofs, Mor Ngom, Luke Bu, Guoyu Liu, Jason T C Lee, Suzan Imren, Vivian Lam, Grace F T Poon, Maryam Ghaedi, Fumio Takei, Keith Humphries, William Jia, Gerald Krystal
Herein we demonstrate that oncolytic herpes simplex virus-1 (HSV-1) potently activates human peripheral blood mononuclear cells (PBMCs) to lyse leukemic cell lines and primary acute myeloid leukemia samples, but not healthy allogeneic lymphocytes. Intriguingly, we found that UV light-inactivated HSV-1 (UV-HSV-1) is equally effective in promoting PBMC cytolysis of leukemic cells and is 1000- to 10 000-fold more potent at stimulating innate antileukemic responses than UV-inactivated cytomegalovirus, vesicular stomatitis virus, reovirus, or adenovirus...
May 26, 2016: Blood
https://www.readbyqxmd.com/read/26905369/development-of-an-oncolytic-hsv-vector-fully-retargeted-specifically-to-cellular-epcam-for-virus-entry-and-cell-to-cell-spread
#13
T Shibata, H Uchida, T Shiroyama, Y Okubo, T Suzuki, H Ikeda, M Yamaguchi, Y Miyagawa, T Fukuhara, J B Cohen, J C Glorioso, T Watabe, H Hamada, H Tahara
Oncolytic herpes simplex virus (HSV) vectors have attracted increasing attention as novel anti-cancer agents. HSV entry is triggered by the binding of glycoprotein D (gD) to its receptors, such as herpesvirus entry mediator or nectin-1. We have recently reported the construction of a fully retargeted HSV platform that incorporates single-chain antibodies (scFv) into gD to mediate entry exclusively via tumor-associated antigens. In this study, we created an scFv directed against epithelial cell adhesion molecule (EpCAM), a recognized carcinoma-associated antigen, and inserted it into the retargeted HSV platform that is ablated for gD recognition of its canonical receptors and contains the entry-enhancing mutations in gB we previously identified...
2016: Gene Therapy
https://www.readbyqxmd.com/read/26645902/turning-killer-into-cure-the-story-of-oncolytic-herpes-simplex-viruses
#14
REVIEW
Shaun Xiaoliu Zhang
Viruses have the intrinsic capability to kill host cells. Even when the initial infection consists of only a few viruses, they can reproduce themselves in large quantities within a short time and quickly spread to nearby cells, causing substantial tissue damage. These same infectious properties become desirable if they can be converted into killer agents with specificity for malignant cells. Cancer virotherapy is doing exactly that by modifying viruses in ways that allow them to replicate in malignant cells but not in normal cells...
November 2015: Discovery Medicine
https://www.readbyqxmd.com/read/26602205/%C3%AE-pk-oncolytic-activity-includes-modulation-of-the-tumour-cell-milieu
#15
Dominique Bollino, Aric Colunga, Baiquan Li, Laure Aurelian
Oncolytic virotherapy is a unique cancer therapeutic that encompasses tumour cell lysis through both virus replication and programmed cell death (PCD) pathways. Nonetheless, clinical efficacy is relatively modest, likely related to the immunosuppressive tumour milieu. Our studies use the herpes simplex virus type 2 (HSV-2)-based oncolytic virus ΔPK that has documented anti-tumour activity associated with virus replication, PCD and cancer stem cell lysis. They are designed to examine whether ΔPK-mediated oncolysis includes the ability to reverse the immunosuppressive tumour microenvironment by altering the balance of cytokines directly secreted by the melanoma cells and to define its mechanism...
February 2016: Journal of General Virology
https://www.readbyqxmd.com/read/26583803/neuroblastomas-vary-widely-in-their-sensitivities-to-herpes-simplex-virotherapy-unrelated-to-virus-receptors-and-susceptibility
#16
P-Y Wang, H M Swain, A L Kunkler, C-Y Chen, B J Hutzen, M A Arnold, K A Streby, M H Collins, B Dipasquale, J R Stanek, J Conner, T H van Kuppevelt, J C Glorioso, P Grandi, T P Cripe
Although most high-risk neuroblastomas are responsive to chemotherapy, relapse is common and long-term survival is < 40%, underscoring the need for more effective treatments. We evaluated the responsiveness of 12 neuroblastoma cell lines to the Δγ134.5 attenuated oncolytic herpes simplex virus (oHSV), Seprehvir (HSV1716), which is currently used in pediatric phase I trials. We found that entry of Seprehvir in neuroblastoma cells is independent of the expression of nectin-1 and the sum of all four known major HSV entry receptors...
February 2016: Gene Therapy
https://www.readbyqxmd.com/read/26257065/genome-wide-lentiviral-shrna-screen-identifies-serine-arginine-rich-splicing-factor-2-as-a-determinant-of-oncolytic-virus-activity-in-breast-cancer-cells
#17
S T Workenhe, T Ketela, J Moffat, B P Cuddington, K L Mossman
Oncolytic human herpes simplex virus type 1 (HSV-1) shows promising treatment efficacy in late-stage clinical trials. The anticancer activity of oncolytic viruses relies on deregulated pathways in cancer cells, which make them permissive to oncolysis. To identify pathways that restrict HSV-1 KM100-mediated oncolysis, this study used a pooled genome-wide short hairpin RNA library and found that depletion of the splicing factor arginine-rich splicing factor 2 (SRSF2) leads to enhanced cytotoxicity of breast cancer cells by KM100...
May 12, 2016: Oncogene
https://www.readbyqxmd.com/read/25686366/establishing-the-lysine-rich-protein-cest-reporter-gene-as-a-cest-mr-imaging-detector-for-oncolytic-virotherapy
#18
Christian T Farrar, Jason S Buhrman, Guanshu Liu, Anne Kleijn, Martine L M Lamfers, Michael T McMahon, Assaf A Gilad, Giulia Fulci
PURPOSE: To (a) evaluate whether the lysine-rich protein (LRP) magnetic resonance (MR) imaging reporter gene can be engineered into G47Δ, a herpes simplex-derived oncolytic virus that is currently being tested in clinical trials, without disrupting its therapeutic effectiveness and (b) establish the ability of chemical exchange saturation transfer (CEST) MR imaging to demonstrate G47Δ-LRP. MATERIALS AND METHODS: The institutional subcommittee for research animal care approved all in vivo procedures...
June 2015: Radiology
https://www.readbyqxmd.com/read/25656776/ultrasound-as-a-method-to-enhance-antitumor-ability-of-oncolytic-herpes-simplex-virus-for-head-and-neck-cancer
#19
S Okunaga, A Takasu, N Meshii, T Imai, M Hamada, S Iwai, Y Yura
Low-intensity ultrasound is a useful method to enhance the delivery of drugs to target cells via a range of mechanisms including the transient formation of micropores in the cell membrane, a process known as sonoporation. The effect of ultrasound on oncolytic herpes simplex virus type-1 (HSV-1) infection in oral squamous cell carcinoma (SCC) was examined. Human SCC cell line SAS and oncolytic HSV-1 RH2, which was deficient in the neurovirulent γ134.5 gene and exhibited cell fusion actions, were used. Cells grown in multi-well plates were infected with HSV-1 and exposed to ultrasound in the presence or absence of microbubbles after an adsorption period...
April 2015: Cancer Gene Therapy
https://www.readbyqxmd.com/read/25460506/an-hsv-2-based-oncolytic-virus-can-function-as-an-attractant-to-guide-migration-of-adoptively-transferred-t-cells-to-tumor-sites
#20
Xinping Fu, Armando Rivera, Lihua Tao, Xiaoliu Zhang
Adoptive T-cell therapy has shown promises for cancer treatment. However, for treating solid tumors, there is a need for improving the ability of the adoptively transferred T cells to home to tumor sites. We explored the possibility of using an oncolytic virus derived from HSV-2, which can actively pull T effector cells to the site of infection, as a local attractant for migration of adoptively transferred T cells. Our data show that intratumoral administration of this virus can indeed attract active migration of the adoptively transferred T cells to the treated tumor...
January 20, 2015: Oncotarget
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