Phase II Clinical Trial of a Granulocyte-Macrophage Colony-Stimulating Factor–Encoding, Second-Generation Oncolytic Herpesvirus in Patients With Unresectable Metastatic Melanoma

Senzer, Neil; Kaufman, Howard L.; Amatruda, Thomas T.; Nemunaitis, Mike; Reid, Tony; Daniels, Gregory A.; González, René; Glaspy, John A.; Whitman, Eric D.; Harrington, Kevin; Goldsweig, Howard; Marshall, Tracey; Love, Colin; Coffin, Robert S.; Nemunaitis, John

doi:10.1200/jco.2009.24.3675

Cited by 538 publications

(452 citation statements)

References 22 publications

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“…Recently, sipuleucel-T (Provenge, Dendreon, Seattle, WA, USA), indicated for patients with metastatic castration-resistant prostate cancer, received FDA's approval as the first therapeutic cancer vaccine. 5 In addition, extensive Phase II clinical trials have demonstrated that the oncolytic herpes simplex virus talimogene laherparepvec (T-Vec, Amgen Inc., Thousand Oaks, CA, USA) 6 and vaccinia virus JX-547 (Pexa-Vec, Jennerex Biotherapeutics, Inc., San Francisco, CA, USA), 7 both of which carry the gene encoding the immunostimulatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), hold great promise for the treatment of advanced cancer patients. Furthermore, cytotoxic T-cell responses directed against oncolytic virus-infected cancer cells have been identified as an essential factor in the process of destruction of cancer.…”

Section: Open Questionsmentioning

confidence: 99%

“…Indeed, the results of clinical trials of the GM-CSF gene-harboring oncolytic vaccinia virus JX-594 and the GM-CSF gene-harboring oncolytic herpes virus talimogene laherparepvec demonstrated that a clinical benefit can be accomplished by combined respective oncolytic activity with the recruitment of immune cells. 6,7,131 The combination of adoptive T-cell therapy with oncolytic viruses is shown to elicit an increased antitumor effect. 131,132 Collectively, the design of combinatorial therapies of oncolytic viruses with immunotherapeutic modalities may 136,137 and (6) directly targets not only the primary tumor but also metastases.…”

Section: Strategies To Enhance the Potentials Of Icd Induced By Oncolmentioning

confidence: 99%

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Multimodal immunogenic cancer cell death as a consequence of anticancer cytotoxic treatments

2013

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Apoptotic cell death generally characterized by a morphologically homogenous entity has been considered to be essentially non-immunogenic. However, apoptotic cancer cell death, also known as type 1 programmed cell death (PCD), was recently found to be immunogenic after treatment with several chemotherapeutic agents and oncolytic viruses through the emission of various danger-associated molecular patterns (DAMPs). Extensive studies have revealed that two different types of immunogenic cell death (ICD) inducers, recently classified by their distinct actions in endoplasmic reticulum (ER) stress, can reinitiate immune responses suppressed by the tumor microenvironment. Indeed, recent clinical studies have shown that several immunotherapeutic modalities including therapeutic cancer vaccines and oncolytic viruses, but not conventional chemotherapies, culminate in beneficial outcomes, probably because of their different mechanisms of ICD induction. Furthermore, interests in PCD of cancer cells have shifted from its classical form to novel forms involving autophagic cell death (ACD), programmed necrotic cell death (necroptosis), and pyroptosis, some of which entail immunogenicity after anticancer treatments. In this review, we provide a brief outline of the well-characterized DAMPs such as calreticulin (CRT) exposure, high-mobility group protein B1 (HMGB1), and adenosine triphosphate (ATP) release, which are induced by the morphologically distinct types of cell death. In the latter part, our review focuses on how emerging oncolytic viruses induce different forms of cell death and the combinations of oncolytic virotherapies with further immunomodulation by cyclophosphamide and other immunotherapeutic modalities foster dendritic cell (DC)-mediated induction of antitumor immunity. Accordingly, it is increasingly important to fully understand how and which ICD inducers cause multimodal ICD, which should aid the design of reasonably multifaceted anticancer modalities to maximize ICD-triggered antitumor immunity and eliminate residual or metastasized tumors while sparing autoimmune diseases.

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Section: Open Questionsmentioning

confidence: 99%

Section: Strategies To Enhance the Potentials Of Icd Induced By Oncolmentioning

confidence: 99%

Multimodal immunogenic cancer cell death as a consequence of anticancer cytotoxic treatments

2013

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“…One-year overall survival rates of 61, 58 and 48% for all patients, all stage IV patients and stage IV M1c patients, respectively. 133 A recently published meta-analysis of 2100 patients with stage IV metastatic melanoma reported a 1-year overall survival rate was 25.5%. The median survival time is 16 þ months for all patients treated with OncoVEX GM-CSF as well as for the stage IV subset; the median survival time in the meta-analysis was 6.2 months (95% confidence interval, 5.9 months to 6.5 months).…”

Section: Herpes Simplex Virus (Hsv)mentioning

confidence: 99%

Clinical development directions in oncolytic viral therapy

Eager

Nemunaitis

2011

Cancer Gene Ther

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Oncolytic virotherapy is an emerging experimental treatment platform for cancer therapy. Oncolytic viruses are replicativecompetent viruses that are engineered to replicate selectively in cancer cells with specified oncogenic phenotypes. Multiple DNA and RNA viruses have been clinically tested in a variety of tumors. This review will provide a brief description of these novel anticancer biologics and will summarize the results of clinical investigation. To date oncolytic virotherapy has shown to be safe, and has generated clinical responses in tumors that are resistant to chemotherapy or radiotherapy. The major challenge for researchers is to maximize the efficacy of these viral therapeutics, and to establish stable systemic delivery mechanisms.

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“…Several HSV-1 vector expressing GM-CSF have been used to treat experimental tumours [140, 160, 192, 201, 202] and some of them are in clinical trials [203-205]. Most of the oncolytic HSVs analyzed have been based on serially passaged laboratory strains of HSV.…”

Section: Hsv-1 Based Vectors For Cancer Gene Therapymentioning

confidence: 99%

“…Moreover, in a model of mouse lymphoma, mice cured with this virus were protected against further tumour challenge [160]. OncoVex has demonstrated promising results both in phase I/II dose escalation study for head and neck squamous cell cancer [204] and in phase II clinical trial for unresectable malignant melanoma [203, 205]. In spite of the promising findings obtained in clinical trials, using OncoVex, the expression of GM-CSF gave contradictory results in different tumour models [206].…”

Section: Hsv-1 Based Vectors For Cancer Gene Therapymentioning

confidence: 99%

HSV Recombinant Vectors for Gene Therapy

Manservigi

Argnani²,

Marconi³

2010

TOVJ

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The very deep knowledge acquired on the genetics and molecular biology of herpes simplex virus (HSV), has allowed the development of potential replication-competent and replication-defective vectors for several applications in human healthcare. These include delivery and expression of human genes to cells of the nervous systems, selective destruction of cancer cells, prophylaxis against infection with HSV or other infectious diseases, and targeted infection to specific tissues or organs. Replication-defective recombinant vectors are non-toxic gene transfer tools that preserve most of the neurotropic features of wild type HSV-1, particularly the ability to express genes after having established latent infections, and are thus proficient candidates for therapeutic gene transfer settings in neurons. A replication-defective HSV vector for the treatment of pain has recently entered in phase 1 clinical trial. Replication-competent (oncolytic) vectors are becoming a suitable and powerful tool to eradicate brain tumours due to their ability to replicate and spread only within the tumour mass, and have reached phase II/III clinical trials in some cases. The progress in understanding the host immune response induced by the vector is also improving the use of HSV as a vaccine vector against both HSV infection and other pathogens. This review briefly summarizes the obstacle encountered in the delivery of HSV vectors and examines the various strategies developed or proposed to overcome such challenges.

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Phase II Clinical Trial of a Granulocyte-Macrophage Colony-Stimulating Factor–Encoding, Second-Generation Oncolytic Herpesvirus in Patients With Unresectable Metastatic Melanoma

Cited by 538 publications

References 22 publications

Multimodal immunogenic cancer cell death as a consequence of anticancer cytotoxic treatments

Multimodal immunogenic cancer cell death as a consequence of anticancer cytotoxic treatments

Clinical development directions in oncolytic viral therapy

HSV Recombinant Vectors for Gene Therapy

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