Talimogene Laherparepvec (T-VEC) for the Treatment of Advanced Melanoma

Johnson, Douglas B.; Puzanov, Igor; Kelley, Mark C.

doi:10.2217/imt.15.35

Cited by 150 publications

(115 citation statements)

References 52 publications

Supporting

Mentioning

105

Contrasting

Unclassified

Order By: Relevance

“…Ongoing human studies are evaluating both DNA and RNA viruses and wild-type agents, as well as modified agents expressing immunostimulatory gene products. Combination with immune-checkpoint inhibitors has swiftly followed, with signals already of increased response rates compared to virus or checkpoint inhibitor alone 182. This follows evidence in a preclinical in vivo melanoma model, the oncolytic Newcastle disease virus, in combination with an anti-CTLA-4 antibody (ipilimumab), that showed enhanced tumor infiltration by activated CD8 + and CD4 + T cells and a reduction in T regs 183.…”

Section: Discussionmentioning

confidence: 72%

Cancer immunotherapy via combining oncolytic virotherapy with chemotherapy: recent advances

Simpson¹,

Relph²,

Harrington³

et al. 2016

View full text Add to dashboard Cite

Oncolytic viruses are multifunctional anticancer agents with huge clinical potential, and have recently passed the randomized Phase III clinical trial hurdle. Both wild-type and engineered viruses have been selected for targeting of specific cancers, to elicit cytotoxicity, and also to generate antitumor immunity. Single-agent oncolytic virotherapy treatments have resulted in modest effects in the clinic. There is increasing interest in their combination with cytotoxic agents, radiotherapy and immune-checkpoint inhibitors. Similarly to oncolytic viruses, the benefits of chemotherapeutic agents may be that they induce systemic antitumor immunity through the induction of immunogenic cell death of cancer cells. Combining these two treatment modalities has to date resulted in significant potential in vitro and in vivo synergies through various mechanisms without any apparent additional toxicities. Chemotherapy has been and will continue to be integral to the management of advanced cancers. This review therefore focuses on the potential for a number of common cytotoxic agents to be combined with clinically relevant oncolytic viruses. In many cases, this combined approach has already advanced to the clinical trial arena.

show abstract

Section: Discussionmentioning

confidence: 72%

Cancer immunotherapy via combining oncolytic virotherapy with chemotherapy: recent advances

Simpson¹,

Relph²,

Harrington³

et al. 2016

View full text Add to dashboard Cite

show abstract

“…In addition, to minimize toxicity and optimize efficacy, GM-CSF can also be locally delivered in the tumor using modified oncolytic herpes viruses (talimogene laherperepvec; T-VEC) to produce GM-CSF. Such oncolytic viruses infect melanoma cells and then directly promote cell death with antigen release, stimulating antitumor immune responses (86). Intratumoral injection of T-VEC in melanoma patients in combination with ipilimumab treatment resulted in a response rate of 50% with a tolerable safety profile in a phase Ib trail.…”

Section: Combinations With Stimulation Of Antigen Presentation and Comentioning

confidence: 99%

Combination Approaches with Immune-Checkpoint Blockade in Cancer Therapy

2016

View full text Add to dashboard Cite

In healthy individuals, immune-checkpoint molecules prevent autoimmune responses and limit immune cell-mediated tissue damage. Tumors frequently exploit these molecules to evade eradication by the immune system. Over the past years, immune-checkpoint blockade of cytotoxic T lymphocyte antigen-4 and programed death-1 emerged as promising strategies to activate antitumor cytotoxic T cell responses. Although complete regression and long-term survival is achieved in some patients, not all patients respond. This review describes promising, novel combination approaches involving immune-checkpoint blockade in the context of the cancer-immunity cycle, aimed at increasing response rates to the single treatments. Specifically, we discuss combinations that promote antigen release and presentation, that further amplify T cell activation, that inhibit trafficking of regulatory T cells or MSDCs, that stimulate intratumoral T cell infiltration, that increase cancer recognition by T cells, and that stimulate tumor killing.

show abstract

“…TVEC has been developed as an intralesional therapy and is injected directly into accessible melanoma lesions. Several clinical trials in humans have demonstrated favorable antitumor responses with TVEC therapy in metastatic melanomas . There is evidence not only for response of the primary tumor to TVEC treatment but also secondary regression of uninjected lesions and the presence of an antitumor immune response .…”

Section: Introductionmentioning

confidence: 99%

Correlates of response and outcomes with talimogene laherperpvec

Zhou

Wang

McKee

et al. 2019

Journal of Surgical Oncology

View full text Add to dashboard Cite

Background and Objectives Patients with in‐transit or limited cutaneous metastatic melanoma may benefit from intralesional injections with talimogene laherparepvec (TVEC), a modified oncolytic herpesvirus. However, its use in patients with adverse prognostic scores in a real‐life clinical setting has not been studied. Methods We performed a two‐center retrospective analysis of 40 patients with metastatic melanoma treated with TVEC from 2015–2017. Demographics, overall response, and survival after therapy were noted. Results Overall, there was a durable response rate of 40%; median progression‐free survival (PFS) was 10.5 months and median overall survival (OS) was not reached. Bulky disease was associated with decreased OS (15.7 months vs not reached, P < .05) and mPFS (2.3 months vs not reached, P < .05), when compared with smaller tumors. Poor performance status (ECOG 2–3) was associated with worse OS (10.2 months vs not reached, P < .05) and PFS (2.1 months vs not reached, P < .05) compared to patients with ECOG 0–1. There was no difference in the outcomes with age greater than 75 or with prior therapies. Adverse events were relatively tolerable. Conclusions These findings demonstrate that TVEC is an effective and safe treatment for metastatic melanoma in a real‐life clinical setting, and suggest parameters to aid in appropriate therapy selection for optimal response.

show abstract

Talimogene Laherparepvec (T-VEC) for the Treatment of Advanced Melanoma

Cited by 150 publications

References 52 publications

Cancer immunotherapy via combining oncolytic virotherapy with chemotherapy: recent advances

Cancer immunotherapy via combining oncolytic virotherapy with chemotherapy: recent advances

Combination Approaches with Immune-Checkpoint Blockade in Cancer Therapy

Correlates of response and outcomes with talimogene laherperpvec

Contact Info

Product

Resources

About