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Talimogene Laherparepvec (T-VEC): A Review of the Recent Advances in Cancer Therapy.

ABSTRACT: 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). With proven efficacy, T-VEC has been evaluated against a variety of other cancer types in a clinical trial setting. In this article, we will provide a review on OVs and the application of T-VEC in melanoma monotherapy and combination therapy. In addition, we will review the recent progress of T-VEC application in other cutaneous cancer types. Moreover, we will briefly describe our experience of T-VEC therapy at City of Hope, aiming to provide more insight for expanding its future application.

SUBMITTER: Zhang T

PROVIDER: S-EPMC9917711 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Talimogene Laherparepvec (T-VEC): A Review of the Recent Advances in Cancer Therapy.

Zhang Tiantian T Jou Tony Hong-Ting TH Hsin Jerline J Wang Zhe Z Huang Kelly K Ye Jian J Yin Holly H Xing Yan Y

Journal of clinical medicine 20230131 3

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 tre ...[more]

PMID: 36769745

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Project description:Simple Summary Talimogene laherparepvec (T-VEC; IMLYGIC®, Amgen Inc.) is the first oncolytic viral immunotherapy to be approved for the local treatment of unresectable metastatic stage IIIB/C–IVM1a melanoma. Its direct intratumoral injection aim to trigger local and systemic immunologic responses leading to tumor cell lysis, followed by release of tumor-derived antigens and subsequent activation of tumor-specific effector T-cells. Its approval has fueled the interest to study its possible sinergy with other immunotherapeutics in preclinical models as well as in clinical contextes. In fact, it has been shown that intratumoral administration of this immunostimulatory agent successfully synergizes with immune checkpoint inhibitors. The objectives of this review are to resume the current state of the art of T-VEC treatment when used in monotherapy or in combination with immune checkpoint inhibitors, describing the strong rationale of its development, the adverse events of interest and the clinical outcome in selected patient’s populations. Abstract Direct intralesional injection of specific or even generic agents, has been proposed over the years as cancer immunotherapy, in order to treat cutaneous or subcutaneous metastasis. Such treatments usually induce an effective control of disease in injected lesions, but only occasionally were able to demonstrate a systemic abscopal effect on distant metastases. The usual availability of tissue for basic and translational research is a plus in utilizing this approach, which has been used in primis for the treatment of locally advanced melanoma. Melanoma is an immunogenic tumor that could often spread superficially causing in-transit metastasis and involving draining lymph nodes, being an interesting model to study new drugs with different modality of administration from normal available routes. Talimogene laherperepvec (T-VEC) is an injectable modified oncolytic herpes virus being developed for intratumoral injection, that produces granulocyte-macrophage colony-stimulating factor (GM-CSF) and enhances local and systemic antitumor immune responses. After infection, selected viral replication happens in tumor cells leading to tumor cell lysis and activating a specific T-cell driven immune response. For this reason, a probable synergistic effect with immune checkpoints inhibition have been described. Pre-clinical studies in melanoma confirmed that T-VEC preferentially infects melanoma cells and exerts its antitumor activity through directly mediating cell death and by augmenting local and even distant immune responses. T-VEC has been assessed in monotherapy in Phase II and III clinical trials demonstrating a tolerable side-effect profile, a promising efficacy in both injected and uninjected lesions, but a mild effect at a systemic level. In fact, despite improved local disease control and a trend toward superior overall survival in respect to the comparator GM-CSF (which was injected subcutaneously daily for two weeks), responses as a single agent therapy have been uncommon in patients with visceral metastases. For this reason, T-VEC is currently being evaluated in combinations with other immune checkpoint inhibitors such as ipilimumab and pembrolizumab, with interesting confirmation of activity even systemically.

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Talimogene Laherparepvec (T-VEC): A Review of the Recent Advances in Cancer Therapy.

Publications

Talimogene Laherparepvec (T-VEC): A Review of the Recent Advances in Cancer Therapy.

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