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Jingjing Song, Feng Zhang, Jiansong Ji, Minjiang Chen, Qiang Li, Qiaoyou Weng, Shannon Gu, Matthew J Kogut, Xiaoming Yang
OBJECTIVE: To validate the feasibility of molecular imaging-monitored intratumoral radiofrequency hyperthermia (RFH) enhanced direct oncolytic virotherapy for hepatocellular carcinoma (HCC). METHODS: This study included in vitro experiments using luciferase-labeled rat HCC cells and in vivo validation experiments on rat models with orthotopic HCCs. Both cells and HCCs in four groups (n = 6/group) were treated by: (1) combination therapy of oncolytic virotherapy (T-VEC) plus RFH at 42 °C for 30 min; (2) oncolytic virotherapy alone; (3) RFH alone; and (4) saline...
February 18, 2019: International Journal of Hyperthermia
J Ressler, R Silmbrod, A Stepan, F Tuchmann, A Cicha, K Uyanik-Ünal, C Hoeller
Talimogene laherparepvec (T-VEC) is a intralesional oncolytic virotherapy, licensed in the European Union (EU) for locoregional advanced melanoma of American Joint Committee on Cancer (AJCC) stages IIIB, IIIC and IVM1a. Organ transplant recipients (OTRs) are so far excluded from all clinical trials dealing with immunotherapies due to the risk of transplant rejection. A 58-year-old caucasian male with a history of a heart and kidney transplantation in 2014 was diagnosed with melanoma (Breslow thickness of 1...
February 18, 2019: British Journal of Dermatology
Andranik Kahramanian, Toshihiko Kuroda, Hiroaki Wakimoto
Herpes simplex virus (HSV) is one of the most extensively studied oncolytic virus platforms. The recent FDA approval of talimogene laherparepvec (T-VEC) has been accelerating translational research of oncolytic HSV (oHSV) as a promising therapeutic for refractory cancers such as glioblastoma, the deadliest primary malignancy in the brain. The large genome size of HSV readily allows arming of oHSV by incorporating therapeutic transgenes within the virus, as exemplified by T-VEC carrying GM-CSF, thereby enhancing the anticancer activity of oHSV...
2019: Methods in Molecular Biology
Viola Franke, Danique M S Berger, W Martin C Klop, Bernies van der Hiel, Bart A van de Wiel, Sylvia Ter Meulen, Michel W J M Wouters, Winan J van Houdt, Alexander C J van Akkooi
Talimogene laherparepvec (T-VEC) is a modified herpes simplex virus, type 1 (HSV-1), which can be administered intralesionally in patients with stage IIIB/C-IVM1a unresectable melanoma (EMA label). The phase 3 OPTiM registration study showed an overall response rate (ORR) of 26%. Since December 2016, 48 eligible patients started treatment at the Netherlands Cancer Institute. We included 26 patients in this study with a follow up time ≥6 months, reporting Overall Response Rate (ORR), Disease Control Rate (DCR), Adverse Events (AE), prior treatment for melanoma and baseline characteristics, documented in a prospectively maintained database...
January 29, 2019: International Journal of Cancer. Journal International du Cancer
Kenjiro Namikawa, Naoya Yamazaki
Melanoma has several clinically and pathologically distinguishable subtypes, which also differ genetically. Mutation patterns vary among different melanoma subtypes, and efficacy of immune-checkpoint inhibitors differs depending on the subtype of melanoma. In spite of the recent revolution of systemic therapies for advanced melanoma, access to innovative agents is still restricted in many countries. This review article aimed to describe the epidemiology and current status of systemic therapies for melanoma in Japan, where melanoma is rare, but access to innovative agents is available...
January 24, 2019: Current Treatment Options in Oncology
Praveen K Bommareddy, Salvatore Aspromonte, Andrew Zloza, Samuel D Rabkin, Howard L Kaufman
Melanoma is an aggressive cutaneous malignancy, but advances over the past decade have resulted in multiple new therapeutic options, including molecularly targeted therapy, immunotherapy, and oncolytic virus therapy. Talimogene laherparepvec (T-VEC) is a herpes simplex type 1 oncolytic virus, and trametinib is a MEK inhibitor approved for treatment of melanoma. Therapeutic responses with T-VEC are often limited, and BRAF/MEK inhibition is complicated by drug resistance. We observed that the combination of T-VEC and trametinib resulted in enhanced melanoma cell death in vitro...
December 12, 2018: Science Translational Medicine
Jonathan G Pol, Sarah Lévesque, Samuel T Workenhe, Shashi Gujar, Fabrice Le Boeuf, Derek R Clements, Jean-Eudes Fahrner, Laetitia Fend, John C Bell, Karen L Mossman, Jitka Fucikova, Radek Spisek, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi
Oncolytic viruses selectively target and kill cancer cells in an immunogenic fashion, thus supporting the establishment of therapeutically relevant tumor-specific immune responses. In 2015, the US Food and Drug Administration (FDA) approved the oncolytic herpes simplex virus T-VEC for use in advanced melanoma patients. Since then, a plethora of trials has been initiated to assess the safety and efficacy of multiple oncolytic viruses in patients affected with various malignancies. Here, we summarize recent preclinical and clinical progress in the field of oncolytic virotherapy...
2018: Oncoimmunology
Satoru Taguchi, Hiroshi Fukuhara, Tomoki Todo
Oncolytic virus therapy is a promising new option for cancer. It utilizes genetically engineered or naturally occurring viruses that selectively replicate in and kill cancer cells without harming normal cells. T-VEC (talimogene laherparepvec), a second-generation oncolytic herpes simplex virus type 1, was approved by the US Food and Drug Administration for the treatment of inoperable melanoma in 2015 and subsequently approved in Europe in 2016. Other oncolytic viruses using different parental viruses have also been tested in Phase III clinical trials and are ready for drug approval: Pexa-Vec (pexastimogene devacirepvec), an oncolytic vaccinia virus, CG0070, an oncolytic adenovirus, and REOLYSIN (pelareorep), an oncolytic reovirus...
November 20, 2018: Japanese Journal of Clinical Oncology
David M Miller, Ryan M Trowbridge, Anupam Desai, Reed E Drews
BACKGROUND: Immune-directed therapies have become front-line therapy for melanoma and are transforming the management of advanced disease. In refractory cases, multi-modal immunoncology (IO) approaches are being utilized, including combining immune checkpoint blockade (ICB) with oncolytic herpes viruses. Talimogene laherparepvec (T-VEC) is the first genetically modified oncolytic viral therapy (OVT) approved for the treatment of recurrent and unresectable melanoma. The use of IO in patients with concomitant malignancies and/or compromised immune systems is limited due to systematic exclusion from clinical trials...
November 19, 2018: Journal for Immunotherapy of Cancer
Ibrahim Ragab Eissa, Itzel Bustos-Villalobos, Toru Ichinose, Shigeru Matsumura, Yoshinori Naoe, Noriyuki Miyajima, Daishi Morimoto, Nobuaki Mukoyama, Wu Zhiwen, Maki Tanaka, Hitoki Hasegawa, Seiji Sumigama, Branko Aleksic, Yasuhiro Kodera, Hideki Kasuya
Oncolytic viral therapy has been accepted as a standard immunotherapy since talimogene laherparepvec (T-VEC, Imlygic® ) was approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for melanoma treatment in 2015. Various oncolytic viruses (OVs), such as HF10 (Canerpaturev-C-REV) and CVA21 (CAVATAK), are now actively being developed in phase II as monotherapies, or in combination with immune checkpoint inhibitors against melanoma. Moreover, in glioma, several OVs have clearly demonstrated both safety and a promising efficacy in the phase I clinical trials...
September 26, 2018: Cancers
Teofila Seremet, Simon Planken, Julia K Schwarze, Yanina Jansen, Laura Vandeweerd, Robbe van den Begin, Ioannis Tsechelidis, Danielle Lienard, Véronique Del Marmol, Bart Neyns
Monoclonal antibodies that block the programmed death-1 (anti-PD-1) or cytotoxic T-lymphocyte antigen-4 (CTLA-4) immune checkpoint receptors (pembrolizumab, nivolumab, ipilimumab, or the combination of nivolumab with ipilimumab) are approved treatment option for patients with advanced melanoma. Over half of all patients are refractory to these immunotherapies and are in need of alternative or complementary treatment options. Talimogene laherparepvec (T-VEC) is a first-in-class intralesionally delivered oncolytic immunotherapy, which has proven efficacy in the treatment of advanced melanoma...
February 2019: Melanoma Research
Claire-Audrey Y Bayan, Adriana T Lopez, Robyn D Gartrell, Kimberly M Komatsubara, Margaret Bogardus, Nisha Rao, Cynthia Chen, Thomas D Hart, Thomas Enzler, Emanuelle M Rizk, Jaya Sarin Pradhan, Douglas K Marks, Larisa J Geskin, Yvonne M Saenger
PURPOSE OF REVIEW: Oncolytic virotherapy is a new approach to the treatment of cancer and its success in the treatment of melanoma represents a breakthrough in cancer therapeutics. This paper provides a review of the current literature on the use of oncolytic viruses (OVs) in the treatment of melanoma. RECENT FINDINGS: Talimogene laherparepvec (T-VEC) is the first OV approved for the treatment of melanoma and presents new challenges as it enters the clinical setting...
August 25, 2018: Current Oncology Reports
Julie M Collins, Jason M Redman, James L Gulley
Multiple immune checkpoint inhibitors (ICIs) that modulate immune cells in the periphery and the tumor microenvironment (TME) have been approved, as have the therapeutic cancer vaccines sipuleucel-T for metastatic castration-resistant prostate cancer and talimogene laherparepvec (T-VEC) for metastatic melanoma. These developments provide rationale for combining these modalities to improve response rates and durability of responses in a variety of cancers. Preclinical data have shown that vaccines can induce immune responses that turn a tumor from 'cold' to 'hot,' but vaccines do not appear to be highly active as monotherapy...
August 2018: Expert Review of Vaccines
Thomas H Long, Michi M Shinohara, Zsolt B Argenyi, John A Thompson, Jennifer M Gardner
Talimogene laherparepvec (T-VEC) is a novel intralesional oncolytic genetically modified herpes simplex virus type 1 vector for the treatment of unresectable cutaneous, subcutaneous, and nodal melanoma. Although immunological therapies such as T-VEC offer therapeutic promise, they carry a risk of immune-related adverse events (irAEs), the full spectrum of which is incompletely understood. We report a 63-year-old previously healthy man with cutaneous melanoma of the right ankle and progressive right lower extremity in-transit metastases despite systemic therapy with immunomodulatory and molecularly targeted treatments...
November 2018: Journal of Cutaneous Pathology
Ludimila Cavalcante, Akansha Chowdhary, Jeffrey A Sosman, Sunandana Chandra
The field of tumor immunology has faced many complex challenges over the last century, but the approval of immune checkpoint inhibitors (anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA4] and anti-programmed cell death-1 [PD-1]/PD-ligand 1 [PD-L1]) and talimogene laherparepvec (T-VEC) for the treatment of metastatic melanoma have awakened a new wave of interest in cancer immunotherapy. Additionally, combinations of vaccines and oncolytic viral therapies with immune checkpoint inhibitors and other systemic agents seem to be promising synergistic strategies to further boost the immune response against cancer...
October 2018: American Journal of Clinical Dermatology
Alexander T Baker, Carmen Aguirre-Hernández, Gunnel Halldén, Alan L Parker
The licensing of talimogene laherparepvec (T-Vec) represented a landmark moment for oncolytic virotherapy, since it provided unequivocal evidence for the long-touted potential of genetically modified replicating viruses as anti-cancer agents. Whilst T-Vec is promising as a locally delivered virotherapy, especially in combination with immune-checkpoint inhibitors, the quest continues for a virus capable of specific tumour cell killing via systemic administration. One candidate is oncolytic adenovirus (Ad); it’s double stranded DNA genome is easily manipulated and a wide range of strategies and technologies have been employed to empower the vector with improved pharmacokinetics and tumour targeting ability...
June 14, 2018: Cancers
Daisuke Watanabe, Fumi Goshima
Oncolytic virotherapy is a kind of antitumor therapy using viruses with natural or engineered tumor-selective replication to intentionally infect and kill tumor cells. An early clinical trial has been performed in the 1950s using wild-type and non-engineered in vitro-passaged virus strains and vaccine strains (first generation oncolytic viruses). Because of the advances in biotechnology and virology, the field of virotherapy has rapidly evolved over the past two decades and innovative recombinant selectivity-enhanced viruses (second generation oncolytic viruses)...
2018: Advances in Experimental Medicine and Biology
Xinping Fu, Lihua Tao, Pin-Yi Wang, Timothy P Cripe, Xiaoliu Zhang
Herpes simplex virus (HSV) is one of the many viruses that have been modified or adapted for oncolytic purposes. There are two serotypes of HSV, HSV-1 and HSV-2. The majority of oncolytic HSVs, including T-VEC which has recently been approved by the US Food and Drug Administration (FDA) for clinical use in treating late stage melanoma patients, are derived from HSV-1. Recently, we and others have developed several HSV-2 based oncolytic viruses. During our in vitro characterization of oncolytic viruses developed from both serotypes (Baco-1 from HSV-1 and FusOn-H2 from HSV-2), we noticed there is a subpopulation of cancer cells in which both viruses could infect but only FusOn-H2 could spread from cell to cell on monolayers...
April 20, 2018: Oncotarget
Lillian Sun, Pauline Funchain, Jung Min Song, Patricia Rayman, Charles Tannenbaum, Jennifer Ko, Michael Mcnamara, C Marcela Diaz-Montero, Brian Gastman
BACKGROUND: Talimogene Laherparepvec (T-VEC) is an oncolytic virus approved as an intratumoral therapy for treating unresectable stage IIIB-IV metastatic melanoma. The mechanisms of action for T-VEC and checkpoint inhibitor are highly complementary. Recent studies have shown that combining checkpoint inhibitor therapy with T-VEC injection can lead to improved response rates for stage IIIB-IV melanoma patients. METHODS: We reviewed 10 consecutive cases of stage IIIC to stage IVM1b melanoma patients that received T-VEC plus checkpoint inhibitor(s) therapy (pembrolizumab, ipilimumab/nivolumab, or nivolumab) treated between June 2016 and August 2017 at the Cleveland Clinic with a median follow-up of 7 months (range: 4 to 13 months)...
May 16, 2018: Journal for Immunotherapy of Cancer
Zoë Blake, Douglas K Marks, Robyn D Gartrell, Thomas Hart, Patti Horton, Simon K Cheng, Bret Taback, Basil A Horst, Yvonne M Saenger
BACKGROUND: Immunotherapy, in particular checkpoint blockade, has changed the clinical landscape of metastatic melanoma. Nonetheless, the majority of patients will either be primary refractory or progress over follow up. Management of patients progressing on first-line immunotherapy remains challenging. Expanded treatment options with combination immunotherapy has demonstrated efficacy in patients previously unresponsive to single agent or alternative combination therapy. CASE PRESENTATION: We describe the case of a patient with diffusely metastatic melanoma, including brain metastases, who, despite being treated with stereotactic radiosurgery and dual CTLA-4/PD-1 blockade (ipilimumab/nivolumab), developed systemic disease progression and innumerable brain metastases...
April 6, 2018: Journal for Immunotherapy of Cancer
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