Talimogene laherparepvec (T-Vec) for the treatment of melanoma and other cancers

Grigg, Claud; Blake, Zoe; Gartrell, Robyn D.; Sacher, Adrian G.; Taback, Bret; Saenger, Yvonne M.

doi:10.1053/j.seminoncol.2016.10.005

Cited by 46 publications

(39 citation statements)

References 55 publications

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“…Since then, due to the decades of basic research on BRAF/MEK and fundamental understanding of the immune response against tumor cell, several therapeutic agents have been approved by the US Food and Drug Administration (FDA) for the treatment of melanoma. These novel agents include immunotherapeutic antibodies targeting cytotoxic T‐lymphocyte‐associated antigen 4 (CTLA‐4) and programmed cell‐death protein 1 (PD‐1), small molecule inhibitors of BRAF or MEK and the modified oncolytic herpes virus talimogene laherparepvec (T‐VEC) which only improves the long‐term benefits in a subset of patients with injectable melanoma lesion in the skin or lymph nodes . Due to these available treatment options, the median OS of patients with advanced melanoma is at least 2 years now …”

Section: Introductionmentioning

confidence: 99%

“…These novel agents include immunotherapeutic antibodies targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell-death protein 1 (PD-1), small molecule inhibitors of BRAF or MEK and the modified oncolytic herpes virus talimogene laherparepvec (T-VEC) which only improves the long-term benefits in a subset of patients with injectable melanoma lesion in the skin or lymph nodes. 4 Due to these available treatment options, the median OS of patients with advanced melanoma is at least 2 years now. 3,5 The long-term benefit of patients with metastatic melanoma has improved significantly because of immunotherapy and BRAF-targeted treatment.…”

Section: Introductionmentioning

confidence: 99%

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Impact of clinicopathological characteristics on survival in patients treated with immune checkpoint inhibitors for metastatic melanoma

Zhao

2018

Intl Journal of Cancer

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Immune checkpoint inhibitors (ICIs) have unprecedented effects on the treatment of metastatic melanoma. However, little is known about the prognostic values of various clinicopathological characteristics. Here, PubMed, Embase and Cochrane database were searched from inception to April 2018 for random controlled trials (RCTs) that compared ICIs with controls. The hazard ratios (HRs) for overall survival (OS) according to gender, age, Eastern Cooperative Oncology Group (ECOG) performance status (PS), lactate dehydrogenase (LDH) level and metastasis stage were extracted. Four phase III RCTs involving 1,598 patients with metastatic melanoma were included in this study. Compared with conventional agents, ICIs were associated with prolonged OS (HR, 0.67; 95% CI, 0.50–0.88; p = 0.005). The pooled OS HR was 0.60 (95% CI, 0.42–0.84; p = 0.003) in men; 0.84 (95% CI, 0.69–1.01; p = 0.07) in women. The difference in efficacy between men and women was significant (pinteraction = 0.03). The OS HR was 0.59 (95% CI, 0.41–0.83; p = 0.003) in patients >65 years old; 0.74 (95% CI, 0.55–1.01; p = 0.054) in patients <65 years old. The OS HR was 0.75 (95% CI, 0.60–0.94; p = 0.01) in patients with ECOG PS = 1; 0.64 (95% CI, 0.38–1.06; p = 0.08) in patients with ECOG PS = 0. Additionally, the long‐term benefits were independent of metastasis stage and LDH level. In summary, although immunotherapy significantly prolongs OS in metastatic melanoma, the long‐term benefits in women, younger patients (<65 years old) and patients with ECOG PS = 0 were marginal. These results may assist in treatment decision‐making, design and interpretation of clinical trials and economic analyses.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impact of clinicopathological characteristics on survival in patients treated with immune checkpoint inhibitors for metastatic melanoma

Zhao

2018

Intl Journal of Cancer

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“…Such viruses can also be "armed" to express therapeutic transgenes, and secrete them from infected tumour cells (Seymour & Fisher, 2016). The first agent to receive an FDA product licence, Imlygic, is an oncolytic herpes virus that expresses human GM-CSF (Grigg et al, 2016). Several oncolytic viruses are currently under development, but one of the most advanced is EnAdenotucirev (EnAd), a chimera of adenovirus type 3 (Ad3) and type 11p (Ad11p), which is currently undergoing clinical evaluation for a range of metastatic carcinoma types (Kuhn et al, 2008;Calvo et al, 2014;Illingworth et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Oncolytic adenovirus expressing bispecific antibody targets T‐cell cytotoxicity in cancer biopsies

et al. 2017

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Oncolytic viruses exploit the cancer cell phenotype to complete their lytic life cycle, releasing progeny virus to infect nearby cells and repeat the process. We modified the oncolytic group B adenovirus EnAdenotucirev (EnAd) to express a bispecific single‐chain antibody, secreted from infected tumour cells into the microenvironment. This bispecific T‐cell engager (BiTE) binds to EpCAM on target cells and cross‐links them to CD3 on T cells, leading to clustering and activation of both CD4 and CD8 T cells. BiTE transcription can be controlled by the virus major late promoter, limiting expression to cancer cells that are permissive for virus replication. This approach can potentiate the cytotoxicity of EnAd, and we demonstrate using primary pleural effusions and peritoneal malignant ascites that infection of cancer cells with the BiTE‐expressing EnAd leads to activation of endogenous T cells to kill endogenous tumour cells despite the immunosuppressive environment. In this way, we have armed EnAd to combine both direct oncolysis and T cell‐mediated killing, yielding a potent therapeutic that should be readily transferred into the clinic.

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“…HSV-1716, G207, and T-VEC are oncolytic HSVs with ICP34.5 deletions. T-VEC has been approved by the US FDA for the treatment of melanoma [113]. In a recent study, the ORR among patients with in-transit melanoma metastasis treated with T-VEC was 40.7% [114].…”

Section: Improving the Safety Of Ovsmentioning

confidence: 99%

Development of oncolytic virotherapy: from genetic modification to combination therapy

et al. 2020

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Oncolytic virotherapy (OVT) is a novel form of immunotherapy using natural or genetically modified viruses to selectively replicate in and kill malignant cells. Many genetically modified oncolytic viruses (OVs) with enhanced tumor targeting, antitumor efficacy, and safety have been generated, and some of which have been assessed in clinical trials. Combining OVT with other immunotherapies can remarkably enhance the antitumor efficacy. In this work, we review the use of wild-type viruses in OVT and the strategies for OV genetic modification. We also review and discuss the combinations of OVT with other immunotherapies.

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Talimogene laherparepvec (T-Vec) for the treatment of melanoma and other cancers

Cited by 46 publications

References 55 publications

Impact of clinicopathological characteristics on survival in patients treated with immune checkpoint inhibitors for metastatic melanoma

Impact of clinicopathological characteristics on survival in patients treated with immune checkpoint inhibitors for metastatic melanoma

Oncolytic adenovirus expressing bispecific antibody targets T‐cell cytotoxicity in cancer biopsies

Development of oncolytic virotherapy: from genetic modification to combination therapy

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