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Talimogene Laherparepvec (T-VEC): An Intralesional Cancer Immunotherapy for Advanced Melanoma. | LitMetric

AI Article Synopsis

  • - Direct intralesional injection of agents like Talimogene laherperepvec (T-VEC) has been explored as a cancer immunotherapy, especially for skin-related metastases, showing effective control in treated lesions, but limited systemic effects on distant metastases.
  • - T-VEC is an engineered herpes virus that targets melanoma cells, promotes immune responses, and can enhance the effect of immune checkpoint inhibitors, demonstrating antitumor activity through direct cell death and immune activation.
  • - Clinical trials indicate that T-VEC has tolerable side effects and shows promising efficacy in both treated and untreated lesions, though as a single-agent therapy, its systemic impact remains mild compared to other treatments like GM-CSF.

Article 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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003308PMC
http://dx.doi.org/10.3390/cancers13061383DOI Listing

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