T-Vec

Oncolytic viruses (OVs) are promising therapeutics for tumors with a poor prognosis. An OV based on herpes simplex virus type 1 (oHSV-1), talimogene laherparepvec (T-VEC), has been recently approved by the Food and Drug Administration (FDA) and by the European Medicines Agency (EMA) for the treatment of unresectable melanoma. T-VEC, like most OVs, is administered via intratumoral injection, underlining the unresolved problem of the systemic delivery of the oncolytic agent for the treatment of metastases and deep-seated tumors...

BACKGROUND: The survival rates for pediatric patients with relapsed and refractory tumors are poor. Successful treatment strategies are currently lacking and there remains an unmet need for novel therapies for these patients. We report here the results of a phase 1 study of talimogene laherparepvec (T-VEC) and explore the safety of this oncolytic immunotherapy for the treatment of pediatric patients with advanced non-central nervous system tumors. METHODS: T-VEC was delivered by intralesional injection at 106 plaque-forming units (PFU)/ml on the first day, followed by 108 PFU/ml on the first day of week 4 and every 2 weeks thereafter...

Keratinocytic cancers (KCs), specifically cutaneous squamous cell and basal cell carcinomas, can respond to topical, intralesional, or systemic immunotherapies, but cutaneous adverse events (CAEs) may occur. Understanding these risks, early recognition of these CAEs, and effective treatment may enable patients to continue their anticancer immunotherapies without dose impact. Immune checkpoint inhibitor-related CAEs after KCs can have multiple clinical presentations, with specific observed types including psoriasis and bullous pemphigoid...

BACKGROUND: Checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) have demonstrated clinical efficacy in advanced melanoma, but only a subset of patients with inflamed tumors are responsive. Talimogene laherparepvec (T-VEC), a modified herpes simplex virus type 1 (HSV-1) expressing granulocyte-macrophage colony-stimulating factor (GM-CSF), is a first-in-class oncolytic immunotherapy approved for the treatment of melanoma and has been shown to inflame the tumor microenvironment...

Talimogene laherparepvec (T-VEC) plus ipilimumab has demonstrated greater antitumor activity versus ipilimumab alone, without additional toxicity, in patients with advanced melanoma. Here, we report the 5-year outcomes from a randomized phase II study. These data provide the longest efficacy and safety follow-up for patients with melanoma treated with a combination of an oncolytic virus and a checkpoint inhibitor.Eligible patients with unresectable stage IIIB‒IV melanoma were randomized 1:1 to receive T-VEC plus ipilimumab or ipilimumab alone...

PURPOSE OF REVIEW: This review presents the rationale for intratumoral immunotherapy, technical considerations and safety. Clinical results from the latest trials are provided and discussed. RECENT FINDINGS: Intratumoral immunotherapy is feasible and safe in a wide range of cancer histologies and locations, including lung and liver. Studies mainly focused on multi-metastatic patients, with some positive trials such as T-VEC in melanoma, but evidence of clinical benefit is still lacking...

Oncolytic viruses (OVs) as one promising antitumor methods have made important contributions to tumor immunotherapy, which arouse increasing attention. They provide the dual mechanisms including direct killing effect toward tumor cells and immune activation for elevating antitumor responses, which have been proved in many preclinical studies. Especially, natural or genetically modified viruses as clinical immune preparations have emerged as a new promising approach objective to oncology treatment. The approval of talimogene laherparepvec (T-VEC) by the U...

Viral vectors have been used for a broad spectrum of gene therapy for both acute and chronic diseases. In the context of cancer gene therapy, viral vectors expressing anti-tumor, toxic, suicide and immunostimulatory genes, such as cytokines and chemokines, have been applied. Oncolytic viruses, which specifically replicate in and kill tumor cells, have provided tumor eradication, and even cure of cancers in animal models. In a broader meaning, vaccine development against infectious diseases and various cancers has been considered as a type of gene therapy...

Mutations in the NRAS gene are common alterations in malignant melanoma. However, there are no specific treatment options approved for NRAS -mutated melanoma patients besides immune checkpoint inhibition. Since preclinical data suggests a synergistic effect of a MEK inhibitor (MEKi) and the oncolytic virus talimogene laherparepvec (T-VEC), we have treated three melanoma patients with this combination. All of the three patients had been suffering from recurring cutaneous and subcutaneous in-transit metastases...

No abstract text is available yet for this article.

Locoregionally advanced and metastatic melanoma are complex diagnoses with a variety of available treatment options. Intralesional therapy for melanoma has been under investigation for decades; however, it has advanced precipitously in recent years. In 2015, the Food and Drug Administration (FDA) approved talimogene laherparepvec (T-VEC), the only FDA-approved intralesional therapy for advanced melanoma. There has been significant progress since that time with other oncolytic viruses, toll-like receptor agonists, cytokines, xanthene dyes, and immune checkpoint inhibitors all under investigation as intralesional agents...

Toll-like receptors (TLRs), which serve as a bridge between innate and adaptive immunity, may be viable treatment targets. TLRs are the first line of defense against microbes and activate signaling cascades that induce immune and inflammatory responses. Patients with "hot" versus "cold" tumors may respond more favorably to immune checkpoint inhibition, and through their downstream effects, TLR agonists have the potential to convert "cold tumors" into "hot tumors" making TLRs in combination with immune checkpoint inhibitors, potential targets for cancer therapies...

Metastatic spinal melanoma is a rare and aggressive disease process with poor prognosis. We review the literature on metastatic spinal melanoma, focusing on its epidemiology, management, and treatment outcomes. Demographics of metastatic spinal melanoma are similar to those for cutaneous melanoma, and cutaneous primary tumors tend to be most common. Decompressive surgical intervention and radiotherapy have traditionally been considered mainstays of treatment, and stereotactic radiosurgery has emerged as a promising approach in the operative management of metastatic spinal melanoma...

BACKGROUND: Talimogene laherparepvec (T-VEC), a first-in-class oncolytic viral immunotherapy, enhances tumor-specific immune activation. T-VEC combined with atezolizumab, which blocks inhibitor T-cell checkpoints, could provide greater benefit than either agent alone. Safety/efficacy of the combination was explored in patients with triple negative breast cancer (TNBC) or colorectal cancer (CRC) with liver metastases. METHODS: In this phase Ib, multicenter, open-label, parallel cohort study of adults with TNBC or CRC with liver metastases, T-VEC (106 then 108 PFU/ml; ≤4 ml) was administered into hepatic lesions via image-guided injection every 21 (±3) days...

No abstract text is available yet for this article.

Immunotherapy has revolutionized treatment of cancer during the last decades. Oncolytic virotherapy has also emerged as a strategy to fight against cancer cells both via lysis of malignant cells and activating immune responses. Accepted as a logical strategy, combination of monoclonal antibodies particularly against the programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) is introduced to improve clinical responses to immune checkpoint inhibitors (ICIs). Accordingly, Talimogene laherparepvec (T-VEC) has received approval for clinical use, while a number of oncolytic Adenoviruses (Ads) are being investigated in clinical trials of malignancies...

The use of immunotherapy in the treatment of advanced and high-risk melanoma has led to a striking improvement in outcomes. Although the incidence of melanoma has continued to rise, median survival has improved from approximately 6 months to nearly 6 years for patients with advanced inoperable stage IV disease. Recent understanding of the tumor microenvironment and its interplay with the immune system has led to the explosive development of novel immunotherapy treatments. Since the approval of the therapeutic cytokines interleukin-2 and interferon alfa-2 in the 1990s, the development of novel immune checkpoint inhibitors (ICIs), oncolytic virus therapy, and modulators of the tumor microenvironment have given way to a new era in melanoma treatment...

Neoadjuvant chemotherapy plus the oncolytic virus T-VEC had a pathologic complete response rate of 45.9%.

The landscape of melanoma treatment has undergone a dramatic revolution in the past decade. The use of oncolytic viruses (OVs) represents a novel therapeutic approach that can selectively infect and lyse tumor cells and induce local and systemic antitumor immune responses. As the first OV approved by the Food and Drug Administration (FDA) for melanoma treatment, talimogene laherparepvec (T-VEC), a genetically modified herpes simplex virus (HSV), has shown promising therapeutic effects in the treatment of advanced melanoma, both as a monotherapy or in combination with other immunotherapies, such as the immune checkpoint inhibitors (ICIs)...

Talimogene laherparepvec (T-VEC) is an oncolytic virus hypothesized to enhance triple-negative breast cancer (TNBC) responses to neoadjuvant chemotherapy (NAC). This article describes the phase 2 trial of T-VEC plus NAC (ClinicalTrials.gov ID: NCT02779855 ). Patients with stage 2-3 TNBC received five intratumoral T-VEC injections with paclitaxel followed by doxorubicin and cyclophosphamide and surgery to assess residual cancer burden index (RCB). The primary end point was RCB0 rate. Secondary end points were RCB0-1 rate, recurrence rate, toxicity and immune correlates...