Novel use of <scp>R</scp>ose <scp>B</scp>engal (<scp>PV</scp>‐10) in two cases of refractory scalp sarcoma

Tan, Clara Y.; Neuhaus, Susan J.

doi:10.1111/ans.12033

Cited by 12 publications

(8 citation statements)

References 3 publications

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“…PV‐10 (Provectus Biopharmaceuticals, Inc., Knoxville, TN) is an injectable formulation of rose bengal disodium, a water‐soluble xanthene dye, designed to be injected into solid tumors. PV‐10 has received orphan drug designation from the U.S. Food & Drug Administration (FDA) for its metastatic melanoma and hepatocellular carcinoma (HCC) indications . After intratumoral injection, PV‐10 accumulates in lysosomes and causes rapid tumor cell lysis, which can potentially induce secondary T cell–mediated systemic antitumor immunity .…”

Section: Intratumoral Immunotherapiesmentioning

confidence: 99%

Intratumoral Immunotherapy—Update 2019

2019

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Intratumoral immunotherapies aim to trigger local and systemic immunologic responses via direct injection of immunostimulatory agents with the goal of tumor cell lysis, followed by release of tumor‐derived antigens and subsequent activation of tumor‐specific effector T cells. In 2019, a multitude of intratumoral immunotherapies with varied mechanisms of action, including nononcolytic viral therapies such as PV‐10 and toll‐like receptor 9 agonists and oncolytic viral therapies such as CAVATAK, Pexa‐Vec, and HF10, have been extensively evaluated in clinical trials and demonstrated promising antitumor activity with tolerable toxicities in melanoma and other solid tumor types. Talimogene laherparepvec (T‐VEC), a genetically modified herpes simplex virus type 1–based oncolytic immunotherapy, is the first oncolytic virus approved by the U.S. Food and Drug Administration for the treatment of unresectable melanoma recurrent after initial surgery. In patients with unresectable metastatic melanoma, T‐VEC demonstrated a superior durable response rate (continuous complete response or partial response lasting ≥6 months) over subcutaneous GM‐CSF (16.3% vs. 2.1%; p < .001). Responses were seen in both injected and uninjected lesions including visceral lesions, suggesting a systemic antitumor response. When combined with immune checkpoint inhibitors, T‐VEC significantly improved response rates compared with single agent; similar results were seen with combinations of checkpoint inhibitors and other intratumoral therapies such as CAVATAK, HF10, and TLR9 agonists. In this review, we highlight recent results from clinical trials of key intratumoral immunotherapies that are being evaluated in the clinic, with a focus on T‐VEC in the treatment of advanced melanoma as a model for future solid tumor indications. Implications for Practice This review provides oncologists with the latest information on the development of key intratumoral immunotherapies, particularly oncolytic viruses. Currently, T‐VEC is the only U.S. Food and Drug Administration (FDA)‐approved oncolytic immunotherapy. This article highlights the efficacy and safety data from clinical trials of T‐VEC both as monotherapy and in combination with immune checkpoint inhibitors. This review summarizes current knowledge on intratumoral therapies, a novel modality with increased utility in cancer treatment, and T‐VEC, the only U.S. FDA‐approved oncolytic viral therapy, for medical oncologists. This review evaluates approaches to incorporate T‐VEC into daily practice to offer the possibility of response in selected melanoma patients with manageable adverse events as compared with other available immunotherapies.

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Section: Intratumoral Immunotherapiesmentioning

confidence: 99%

Intratumoral Immunotherapy—Update 2019

2019

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“…This photosensitizing drug has been reported to be an effective therapeutic agent against melanoma 23 and, more recently, against sarcoma. 24 Photosensitizing drugs work via photochemical reactions that produce toxic products, such as reactive oxygen species, which can bring about cell death. 16 The cytotoxicity of illuminated photosensitizers in the presence of oxygen has been known for a long time.…”

Section: ■ Discussionmentioning

confidence: 99%

Mitochondrial Routing of Glucose and Sucrose Polymers after Pinocytotic Uptake: Avenues for Drug Delivery

et al. 2014

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Mitochondria are key organelles organizing cellular metabolic flux. Therefore, a targeted drug delivery to mitochondria promises the advancement of medicine in fields that are associated with mitochondrial dysfunction. However, successful mitochondrial drug delivery is limited by complex transport steps across organelle membranes and fast drug efflux in cases of multidrug resistance. Strategies to deliver small-molecular-weight drugs to mitochondria are very limited, while the use of complex polymeric carriers is limited by a lack of clinical feasibility. We show here that clinically established macromolecules such as a sucrose copolymer (Ficoll 70/400 kDa) and polyglucose (dextran 70/500 kDa) are micropinocytosed swiftly by mesenchymal stem cells and subsequently routed to mitochondria. The intracellular level of Ficoll appears to decrease over time, suggesting that it does not persist within cells. After coupling to polysucrose, the low-molecular-weight photodynamic drug Rose Bengal reached mitochondria and thus exhibited an increased destructive potential after laser excitation. These findings support new opportunities to deliver already clinically approved drugs to mitochondria.

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“…The 10% rose bengal solution is a water-soluble stain used to diagnose liver and eye cancers and ocular damage, as well as in food coloring in Japan and as an insecticide, with medical reports being published as early as the 1920s. 37,60 Because of the wide variety of its application, experience with the drug is extensive, and its safety profile has been well established. 12,13,23,37 As an xanthine dye, the hypothesized mechanism of action of 10% rose bengal is that it creates reactive oxygen by reacting with visible and ultraviolet light, thereby mediating phototoxic reactions.…”

Section: Rose Bengalmentioning

confidence: 99%

“…The rate of morbidity is generally considered to be low, although most patients report some local adverse events, most commonly pain (≤ 80%). 60 Local blistering 40%) has been correlated with a better outcome. 60 Other reported adverse events include vesicles, edema, skin discoloration, inflammation, headache, and pruritus around the treatment site.…”

Section: Rose Bengalmentioning

confidence: 99%

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Developments in Intralesional Therapy for Metastatic Melanoma

Sloot

Rashid

Sarnaik³

et al. 2016

Cancer Control

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Background Locoregional advanced melanoma poses a complex clinical challenge that requires a multidisciplinary, patient-centered approach. Numerous agents have been studied for their suitability as intralesional therapy in the past decades, but few have successfully completed phase 3 clinical trial testing. Methods The relevant medical literature was searched for articles regarding use of intralesional therapies in metastatic melanoma. Therapies with data from phase 2 or higher studies were selected for review. This review also summarizes the mechanisms of action, adverse-event profiles, and clinical data for these agents. Results Intralesional therapies demonstrate promising effects in select patients and are a valuable asset to the current treatment options in advanced melanoma. The optimal approach should be tailored to the individual patient and consists of a combination of intralesional therapies, regional perfusions, systemic immunotherapies, targeted therapies and/or surgery. Conclusions Due to relatively good local response rates and tolerable adverse-event profile, intralesional therapy may be a treatment option for patients with unresectable locally advanced or metastatic melanoma.

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Novel use of Rose Bengal (PV‐10) in two cases of refractory scalp sarcoma

Cited by 12 publications

References 3 publications

Intratumoral Immunotherapy—Update 2019

Intratumoral Immunotherapy—Update 2019

Mitochondrial Routing of Glucose and Sucrose Polymers after Pinocytotic Uptake: Avenues for Drug Delivery

Developments in Intralesional Therapy for Metastatic Melanoma

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