Intratumoral injection of OK-432 suppresses metastatic squamous cell carcinoma lesion inducing interferon-γ and tumour necrosis factor-α

Akeda, Tomoko; Yamanaka, K.; Kitagawa, Hiroshi; Kawabata, E.; Tsuda, K.; Kakeda, Masato; Omoto, Yoko; Habe, Koji; Isoda, Kenichi; Kurokawa, Ichiro; Mizutani, Hideki

doi:10.1111/j.1365-2230.2011.04151.x

Cited by 7 publications

(8 citation statements)

References 2 publications

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“…Incorporation of the LPS and E6020 to Paclitaxel, whole cell tumor cell vector, and Trastuzumab improved the anti-tumor immunity in mouse models (71–73). Picibanil (OK-432) targets both TLR2 and TLR4 and suppresses cancer (74). Vacchelli et al recently published a detailed review of the ongoing clinical trials on TLR modulators, including TLR4 agonists.…”

Section: Potential Of Tlr4 Immunomodulation For the Prevention Or Trementioning

confidence: 99%

Toll-Like Receptor-4 Modulation for Cancer Immunotherapy

Awasthi

2014

Front. Immunol.

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Section: Potential Of Tlr4 Immunomodulation For the Prevention Or Trementioning

confidence: 99%

Toll-Like Receptor-4 Modulation for Cancer Immunotherapy

Awasthi

2014

Front. Immunol.

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“…In addition, intratumoral delivery can achieve significantly higher drug concentrations at the site of action than systemic delivery. In the clinical setting, intratumoral administration has been used to deliver gene therapy constructs, complex biologics, and small molecules to a variety of cancers including adenoviral based p53 genes in head and neck cancer (33); TNFalpha genes in rectal cancer (34); interleukin-2 in melanoma (35); immunostimulant CpG in brain cancers (36); single treatment of a meta-static squamous cell carcinoma lesion (37); BCNU in combination with radiotherapy in glioma (38); and para-toluenesulfonamide in non-small cell lung cancer (39). Intratumoral delivery has been used in the preclinical evaluation of siRNAs (40) and immune modulators (41, 42) as well as to reduce the toxicity of approved agents such as melphalan (43); 2-deoxy- D -glucose alone and in combination with carboplatin (44); and paclitaxel/docetaxel in mammary, bladder, prostate, and head and neck cancers (45–48).…”

Section: Introductionmentioning

confidence: 99%

In Vivo Screening of S100B Inhibitors for Melanoma Therapy

Zimmer

Lapidus

Weber

2012

Methods in Molecular Biology

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S100 proteins are markers for numerous cancers, and in many cases high S100 protein levels are a prognostic indicator for poor survival. One such case is S100B, which is overproduced in a very large percentage of malignant melanoma cases. Elevated S100B protein was more recently validated to have causative effects towards cancer progression via down-regulating the tumor suppressor protein, p53. Towards eliminating this problem in melanoma, targeting S100B with small molecule inhibitors was initiated. This work relies on numerous chemical biology technologies including structural biology, computer-aided drug design, compound screening, and medicinal chemistry approaches. Another important component of drug development is the ability to test compounds and various molecular scaffolds for their efficacy in vivo. This chapter briefly describes the development of S100B inhibitors, termed SBiXs, for melanoma therapy with a focus on the inclusion of in vivo screening at an early stage in the drug discovery process.

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“…Immunotherapy as intratumoral therapy has also been investigated: (a) Propionibacterium acnes induces immunestimulation by increasing interleukin-12, tumor necrosis factor-α, and interferon-γ,77 (b) secondary lymphoid chemokine and unmethylated cytosine-phosphorothioate-guanine-oligodeoxynucleotide were used to mobilize lymphocytes and dendritic cells and increased the infiltration of CD4 + T-cells and CD11c + cells in the tumor mass with observed reduction in tumor mass,78 (c) hu14.18-interleukin-2 administration resulted in increased natural killer (NK) group 2, member D receptors on intratumoral NKG2A/C/E + NKp46 + NK cells,79 (d) OK-432 efficiently suppressed metastatic squamous cell carcinoma lesion by inducing interferon-γ and tumor necrosis factor-α,80 (e) pre-treatment with cyclophosphamide and oligodeoxynucleotides plus rituximab enhanced immune activation against tumor cells and reduced tumor evolution,81 (f) dendritic cells and dendritic cells plus cyclophosphamide or paclitaxel at low doses enhanced immune system activation,82,83 (g) anti-gal antibody injection 84. Furthermore, several biomarkers were used specifically in intratumoral therapies as independent predictive factors, such as T cells and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, an inhibitor of lovastatin, as a formulation that blocks local metastasis after irradiation 85…”

Section: Discussionmentioning

confidence: 99%

Intratumoral chemotherapy for lung cancer: re-challenge current targeted therapies

Hohenforst-Schmidt¹,

Zarogoulidis²,

Darwiche³

et al. 2013

DDDT

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Strategies to enhance the already established doublet chemotherapy regimen for lung cancer have been investigated for more than 20 years. Initially, the concept was to administer chemotherapy drugs locally to the tumor site for efficient diffusion through passive transport within the tumor. Recent advances have enhanced the diffusion of pharmaceuticals through active transport by using pharmaceuticals designed to target the genome of tumors. In the present study, five patients with non-small cell lung cancer epidermal growth factor receptor (EGFR) negative stage IIIa–IV International Union Against Cancer 7 (UICC-7), and with Eastern Cooperative Oncology Group (ECOG) 2 scores were administered platinum-based doublet chemotherapy using combined intratumoral-regional and intravenous route of administration. Cisplatin analogues were injected at 0.5%–1% concentration within the tumor lesion and proven malignant lymph nodes according to pretreatment histological/cytological results and the concentration of systemic infusion was decreased to 70% of a standard protocol. This combined intravenous plus intratumoral-regional chemotherapy is used as a first line therapy on this short series of patients. To the best of our knowledge this is the first report of direct treatment of involved lymph nodes with cisplatin by endobronchial ultrasound drug delivery with a needle without any adverse effects. The initial overall survival and local response are suggestive of a better efficacy compared to established doublet cisplatin–based systemic chemotherapy in (higher) standard concentrations alone according to the UICC 7 database expected survival. An extensive search of the literature was performed to gather information of previously published literature of intratumoral chemo-drug administration and formulation for this treatment modality. Our study shows a favorable local response, more than a 50% reduction, for a massive tumor mass after administration of five sessions of intratumoral chemotherapy plus two cycles of low-dose intravenous chemotherapy according to our protocol. These encouraging results (even in very sick ECOG 2 patients with central obstructive non-small cell lung cancer having a worse prognosis and quality of life than a non-small cell lung cancer in ECOG 0 of the same tumor node metastasis [TNM]-stage without central obstruction) for a chemotherapy-only protocol that differs from conventional cisplatin-based doublet chemotherapy by the route, target site, and dose paves the way for broader applications of this technique. Finally, future perspectives of this treatment and pharmaceutical design for intratumoral administration are presented.

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Intratumoral injection of OK-432 suppresses metastatic squamous cell carcinoma lesion inducing interferon-γ and tumour necrosis factor-α

Cited by 7 publications

References 2 publications

Toll-Like Receptor-4 Modulation for Cancer Immunotherapy

Toll-Like Receptor-4 Modulation for Cancer Immunotherapy

In Vivo Screening of S100B Inhibitors for Melanoma Therapy

Intratumoral chemotherapy for lung cancer: re-challenge current targeted therapies

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