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Recombinant DNA Technology and Gene Therapy Using Viruses
Published in Patricia G. Melloy, Viruses and Society, 2023
IMLYGIC, also known as talimogene laherparepvec, is a melanoma treatment that uses a modified herpesvirus (Lostroh 2019; Anguela and High 2019; Lee et al. 2017; Shahryari et al. 2019). It should be noted that IMLYGIC was the first oncolytic virus treatment approved in the United States back in 2015 (Anguela and High 2019).
Melanoma
Published in Debjani Sahni, Adam Lerner, Bilal Fawaz, Advanced Skin Cancer, 2022
Until recently, treatment of metastatic melanoma was mostly palliative with chemotherapy and/or radiation. Since 2011, the approval of several targeted therapies and immune checkpoint inhibitors has revolutionized the field of melanoma therapeutics and significantly improved the survival of metastatic melanoma patients.13 Agents used for targeted therapy include BRAF inhibitors (e.g., dabrafenib) and MEK inhibitors (e.g., trametinib). Immune checkpoint inhibitor therapeutic agents include cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) inhibitors (e.g., ipilimumab) and programmed cell death 1 (PD-1) inhibitors (e.g., pembrolizumab).4 Other recently approved modalities include Talimogene Laherparepvec (T-VEC), which is a modified oncolytic herpes simplex virus type 1 (HSV-1) having the capacity to express granulocyte macrophage colony-stimulating factor (GM-CSF). T-VEC is approved as intralesional therapy for use in inoperable metastases that are accessible to injection.13,14
Immunomodulatory Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Talimogene laherparepvec (ImlygicTM), which is the first and only genetically modified oncolytic viral therapy for injection directly into melanoma tumors, was approved by the FDA in 2015 for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery.
Is single versus combination therapy problematic in the treatment of cutaneous melanoma?
Published in Expert Review of Clinical Pharmacology, 2021
Regina Krattinger, Egle Ramelyte, Joëlle Dornbierer, Reinhard Dummer
Besides systemic immunotherapy, locally applied agents regulating the immune milieu within the tumor microenvironment are also implemented in treatment of melanoma. Talimogene laherparepvec (T-VEC) is an oncolytic herpes virus, which selectively replicates in tumor cells, where it promotes lytic cell death complemented by release of tumor-derived antigens and granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF enhances a systemic T cell-mediated antitumor immune response by induction of dendritic cell maturation and activation of T cells [29–31]. Intratumorally applied T-VEC resulted in a higher durable response rate (>6 months) and longer median OS as compared to subcutaneously applied GM-CSF (16.3% (95% CI 12.1–20.5) versus 2.1% (95% CI 0–4.5%) and 23.3 months (95% CI 19.5–29.6) versus 18.9 months (95% CI 16.0–23.7), respectively), particularly in treatment-naïve patients with stage IIIB/C or IVM1a (HR 0.57, 95% CI 0.40–0.80). Additionally, administration of T-VEC showed low toxicity, with most common adverse events (AEs) such as fatigue, chills, and pyrexia [32].
Trial watch: intratumoral immunotherapy
Published in OncoImmunology, 2021
Juliette Humeau, Julie Le Naour, Lorenzo Galluzzi, Guido Kroemer, Jonathan G. Pol
Systemic immunotherapies have demonstrated their efficacy to induce durable antitumor immune responses and to increase overall survival (OS) in several solid cancers.77 Yet, a majority of patients experience adverse events which can lead to treatment disruption. Moreover, the immunosuppressive tumor microenvironment efficiently shields off infiltration by cellular mediators of cancer immunosurveillance, thus frequently resulting in the inefficiency of systemic immunotherapies. Preclinical studies have demonstrated that local delivery of immunostimulatory products, such as OVs, cytokines, and PRR agonists could overcome the resistance to systemic immune checkpoint blockade therapies.78–81 These observations have precipitated the evaluation of intratumoral (i.t.) immunotherapy in the clinic.82,83 This dynamic has been supported in 2015 by the FDA approval of talimogene laherparepvec (T-VEC) for i.t. oncolytic virotherapy of melanoma.84,85
Treatment patterns of malignant melanoma in the United States from 2011 to 2016: a retrospective cohort study
Published in Current Medical Research and Opinion, 2020
Shweta Shah, Leon Raskin, David Cohan, Morganna Freeman, Omid Hamid
Before 2011, none of the available drug treatments for malignant melanoma demonstrated improvements in overall survival and were primarily limited to interleukins and cytotoxic chemotherapy. The advent of new systemic and intralesional therapies after 2011 has had a dramatic impact on the treatment landscape5. A number of immune checkpoint inhibitors have been approved since 20116, including ipilimumab (2011)7, pembrolizumab (2014)8, and nivolumab (2014)9. Similarly, a number of drug approvals have been granted for targeted agents inhibiting BRAF, including vemurafenib (2011)10, dabrafenib (2013)11, and encorafenib (2018)12, both as monotherapies and combined with targeted inhibitors of MEK: trametinib (2013)13, cobimetinib (2015)14, and binimetinib (2018)15. The intralesional oncolytic immunotherapy talimogene laherparepvec was approved in 201516.