Impact of novel oncolytic virus HF10 on cellular components of the tumor microenviroment in patients with recurrent breast cancer

Sahin, Tevfik Tolga; Kasuya, Hideki; Nomura, Naohiro; Shikano, Takaaki; Yamamura, Kazuo; Tan, Gewen; Kanzaki, Akiyuki; Fujii, Tsutomu; Sugae, Takashi; Imai, Tsuneo; Nomoto, Shuji; Takeda, Shin; Sugimoto, Hiroyuki; Kikumori, Toyone; Kodera, Yasuhiro; Nishiyama, Yukihiro; Nakao, Akimasa

doi:10.1038/cgt.2011.80

Cited by 54 publications

(41 citation statements)

References 73 publications

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“…(45) UL56 is a gamma accessory gene which is involved in the pathogenicity and latency of HSV-1 and loss of UL56 in HF10 significantly decreases neuroinvasiveness of the virus. (45) It also lacks latency associated transcripts (LATs), which play a role in the reactivation of the HSV-1 virus. (45)…”

Section: Oncolytic Viruses Used In the Treatment Of Melanomamentioning

confidence: 99%

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The Role of Oncolytic Viruses in the Treatment of Melanoma

et al. 2018

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Talimogene laherparepvec (T-VEC) is the first OV approved for the treatment of melanoma and presents new challenges as it enters the clinical setting. Several other OVs are at various stages of clinical and pre-clinical development for the treatment of melanoma. Reports from phase Ib-III clinical trials combining T-VEC with checkpoint blockade are encouraging and demonstrate potential added benefit of combination immunotherapy. OVs have recently emerged as a standard treatment option for patients with advanced melanoma. Several OVs and therapeutic combinations are in development. Immunooncolytic virotherapy combined with immune checkpoint inhibitors is promising for the treatment of advanced melanoma.

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Section: Oncolytic Viruses Used In the Treatment Of Melanomamentioning

confidence: 99%

“…(45) It also lacks latency associated transcripts (LATs), which play a role in the reactivation of the HSV-1 virus. (45)…”

Section: Oncolytic Viruses Used In the Treatment Of Melanomamentioning

confidence: 99%

The Role of Oncolytic Viruses in the Treatment of Melanoma

et al. 2018

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“…Similarly, increased intratumoral T cells were observed in a Phase I trial of oncolytic measles virus involving patients with cutaneous T cell lymphoma, although it was not determined in this case whether these were virus or tumor‐specific . In patients with recurrent metastatic breast cancer, injection of a spontaneously mutated HSV‐1 variant, HF10, triggered intratumoral CD8 + T cell infiltration . In a Phase I trial of a GM‐CSF‐encoding vaccinia virus in patients with refractory melanoma, there was evidence of CD4 + and CD8 + T cell infiltration in injected lesions .…”

Section: Oncolytic Viruses and T Cellsmentioning

confidence: 99%

Solid Tumor Immunotherapy with T Cell Engager‐Armed Oncolytic Viruses

Scott

Duffy

Freedman

et al. 2017

Macromolecular Bioscience

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Oncolytic viruses (OVs) are novel anticancer agents that combine direct cancer cell killing with the stimulation of antitumor immunity. In addition, OVs can be engineered to deliver biological therapeutics directly to tumors, offering unique opportunities to design multimodal anticancer strategies. Here, a case for arming OVs with bispecific T cell engagers (BiTEs) is put forward. BiTEs redirect the cytotoxicity of polyclonal T cells to target cells of choice, and have demonstrated efficacy against a number of hematological cancers. However, the success of BiTEs in the treatment of solid tumors appears more limited, at least in part due to: (i) poor delivery kinetics and penetration into tumors, and (ii) on‐target off‐tumor activity, leading to dose‐limiting toxicities. Linking the production of BiTEs to OV replication provides an exciting means to restrict production to the tumor site, widen their therapeutic window, and synergize with direct oncolysis. This review summarizes progress thus far in the preclinical development of BiTE‐armed OVs, and explores the possibility of cotargeting cancer cells and nontransformed stromal cells.

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“…The spontaneously occurring attenuated HSV-1 mutant HF10 has strong anti-tumor activity in human and mouse breast cancer cell lines, and induces tumor immunity in animal models. In the clinic HF10 has induced tumor immunity in patients with recurrent breast cancer, and lysis of cutaneous metastases in breast cancer patients 9 . Compared with other HSV-1 mutants such as hrR3 that exert cytopathic effect, HF10 induces syncytia formation.…”

Section: Oncolytic Hsv-1 As a Therapeutic Option For Meningeal Metastmentioning

confidence: 99%

HSV-1 as a novel therapy for breast cancer meningeal metastases

Kuruppu

Tanabe

2015

Cancer Gene Ther

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Meningeal metastasis is a fatal complication of breast cancer that affects 5–8 % of patients. When cancer cells seed in the meninges their subsequent growth results in severe neurological complications involving the cranial nerves, cerebrum and spinal cord, limiting life expectancy to less than 4 months. The incidences of meningeal metastases increase with prolonged life span resulting from treatment advances for primary breast cancer and their metastases. Currently there is no cure. Aggressive multimodal therapies such as radiation, chemotherapy (intra-CSF and systemic) are ineffective. Therapeutic agents are often quickly cleared from the CSF, while higher doses that can achieve a therapeutic response are highly toxic. The secure guarding of the subarachnoid space by the blood-brain-barrier on one side and the blood-CSF barrier on the other prevents chemotherapy from reaching the cancer cells in the meninges. These challenges with treating meningeal metastases highlight the urgent need for a new therapeutic modality. An ideal treatment would be an agent that avoids rapid clearance, remains within the CSF, reaches the meninges and selectively destroys tumor cells. Replication conditional oncolytic HSV-1 may be effective in this regard. Viral oncolysis, the destruction of cancer cells by replicating virus is under clinical investigation for cancers that are unresponsive to current therapies. It is based on the model of multiple cycles of lytic virus replication in cancer cells that amplify the injected dose. The therapeutic potential of oncolytic HSV-1 for breast cancer meningeal metastases is discussed here. HSV-1 could be a potential novel treatment for meningeal metastases that can be translated to the clinic.

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Impact of novel oncolytic virus HF10 on cellular components of the tumor microenviroment in patients with recurrent breast cancer

Cited by 54 publications

References 73 publications

The Role of Oncolytic Viruses in the Treatment of Melanoma

The Role of Oncolytic Viruses in the Treatment of Melanoma

Solid Tumor Immunotherapy with T Cell Engager‐Armed Oncolytic Viruses

HSV-1 as a novel therapy for breast cancer meningeal metastases

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