High hydrostatic pressure (HHP) has been shown to induce immunogenic cell death of cancer cells, facilitating their uptake by dendritic cells (DC) and subsequent presentation of tumor antigens. In the present study, we demonstrated immunogenicity of the HHP-treated tumor cells in mice. HHP was able to induce immunogenic cell death of both TC-1 and TRAMP-C2 tumor cells, representing murine models for human papilloma virus-associated tumors and prostate cancer, respectively. HHP-treated cells induced stronger immune responses in mice immunized with these tumor cells, documented by higher spleen cell cytotoxicity and increased IFNγ production as compared to irradiated tumor cells, accompanied by suppression of tumor growth in vivo in the case of TC-1 tumors, but not TRAMP-C2 tumors. Furthermore, HHP-treated cells were used for DC-based vaccine antigen pulsing. DC co-cultured with HHP-treated tumor cells and matured by a TLR 9 agonist exhibited higher cell surface expression of maturation markers and production of IL-12 and other cytokines, as compared to the DC pulsed with irradiated tumor cells. Immunization with DC cell-based vaccines pulsed with HHP-treated tumor cells induced high immune responses, detected by increased spleen cell cytotoxicity and elevated IFNγ production. The DC-based vaccine pulsed with HHP-treated tumor cells combined with docetaxel chemotherapy significantly inhibited growth of both TC-1 and TRAMP-C2 tumors. Our results indicate that DC-based vaccines pulsed with HHP-inactivated tumor cells can be a suitable tool for chemoimmunotherapy, particularly with regard to the findings that poorly immunogenic TRAMP-C2 tumors were susceptible to this treatment modality.

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We recently demonstrated that brain endothelial cells and astrocytes protect cancer cells from chemotherapy through an endothelin-dependent signaling mechanism. Here, we evaluated the efficacy of macitentan, a dual endothelin receptor (ETAR and ETBR) antagonist, in the treatment of experimental breast and lung cancer brain metastases.
The effect of macitentan on astrocyte- and brain endothelial cell-mediated chemoprotective properties was measured in cytotoxic assays. We compared survival of mice bearing established MDA-MB-231 breast cancer or PC-14 non-small cell lung cancer (NSCLC) brain metastases that were treated with vehicle, macitentan, paclitaxel, or macitentan plus paclitaxel. Cell division, apoptosis, tumor vasculature, and expression of survival-related proteins were assessed by immunofluorescent microscopy.
Cancer cells and tumor-associated endothelial cells expressed activated forms of AKT and MAPK in vehicle- and paclitaxel-treated groups in both metastasis models, but these proteins were downregulated in metastases of mice that received macitentan. The survival-related proteins Bcl2L1, Gsta5, and Twist1 that localized to cancer cells and tumor-associated endothelial cells in vehicle- and paclitaxel-treated tumors were suppressed by macitentan. Macitentan or paclitaxel alone had no effect on survival. However, when macitentan was combined with paclitaxel, we noted a significant reduction in cancer cell division and marked apoptosis of both cancer cells and tumor-associated endothelial cells. Moreover, macitentan plus paclitaxel therapy significantly increased overall survival by producing complete responses in 35 of 35 mice harboring brain metastases.
Dual antagonism of ETAR and ETBR signaling sensitizes experimental brain metastases to paclitaxel and may represent a new therapeutic option for patients with brain metastases.
© The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: [email protected].

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Monoclonal antibodies (mAbs) have revolutionized the diagnosis and treatment of many human diseases and the application of combinations of mAbs has demonstrated improved therapeutic activity in both preclinical and clinical testing. Combinations of antibodies have several advantages such as the capacities to target multiple and mutating antigens in complex pathogens and to engage varied epitopes on multiple disease-related antigens (e.g. receptors) to overcome heterogeneity and plasticity. Oligoclonal antibodies are an emerging therapeutic format in which a novel antibody combination is developed as a single drug product. Here, we will provide historical context on the use of oligoclonal antibodies in oncology and infectious diseases and will highlight practical considerations related to their preclinical and clinical development programs.
Copyright © 2016 Elsevier Ltd. All rights reserved.

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On March 21, 2016 Virogin Biotech reported the completion of A-round common share financing for a total of $7 million (USD) on March 16th 2016 (Press release, Virogin Biotech, MAR 21, 2016, View Source [SID1234518862]).

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Virogin Biotech Ltd. specializes in anti-cancer drug research with a focus on innovative anti-cancer vaccines through the use of oncolytic viruses carrying immune stimulating factors. The financing was led by GP Capital Investment Fund with co-investors Shen Zhen Sangel Asset Management Ltd, Purity Star Ltd, Dahua Investment Company and Top Fortune Ventures Ltd, wherein GP Capital and Shen Zhen Sangel were the angel investors of Virogin, and Purity Star, Dahua and Top Fortune Ventures are new investors. The continued financial support of previous investors, alongside new entrants, reflects investor confidence in Virogin’s continuing development.

Virogin is planning to use the proceeds in three areas: the completion of pre-clinical research for our next generation oncolytic virus, expanding our global clinical development team and its capabilities, and enhancing our production capacity to meet clinical needs.

Virogin’s co-founder and CSO Dr. William Jia said: "Virogin’s novel oncolytic virus products represent the next generation of oncolytic viruses, which are enhanced both in oncolytic activity and tumor specificity. At present, Virogin’s product line has progressed smoothly and since June of last year, Virogin has applied for several U.S. Patents. The success of A-round financing ensures Virogin’s momentum for high-speed development and helps to accelerate our products into clinical trials. "

"We are pleased with the continued support from our angel investors; moreover, we are appreciative for the support from our new investors, who include the founders of a listed large-cap company and the founder of an investment fund in the vaccine industry" said Mr. Chris Huang, co-founder and CEO of Virogin. "To bring renewed hope to millions of helpless cancer patients with innovative anti-tumor immunotherapy is Virogin’s dream, and this dream is shared by our investors. We are confident that in the near future we will bring our first oncolytic virus product to phase I clinical trials."

GP Capital Investment Fund founder and president Dongmei Ji said, "We witnessed the establishment of Virogin. It is a wonderful experience to accompany the growth of a company. In this process, you can feel the passion and unlimited vitality of a company. As fund managers, we are pleased to allocate our funds and resources to a promising company with a good research team and technology like Virogin."

Dr. Fangfeng, a partner in Sangel Capital said: "Immunotherapy is the future direction of anti-tumor development; from the very beginning, we are confident in Virogin’s cutting edge technology and the ability of Virogin’s science team. We are very pleased with Virogin’s rapid growth and we will continue to support Virogin in developing its innovative anti-tumor immunology drug."

The Pim proteins (1, 2 and 3) are serine/threonine kinases that have been found to be upregulated in many hematological malignancies and solid tumors. As a result of overlapping functions among the three isoforms, inhibition of all three Pim kinases has become an attractive strategy for cancer therapy. Herein we describe our efforts in identifying potent pan-PIM inhibitors that are derived from our previously reported pyridyl carboxamide scaffold as part of a medicinal chemistry strategy to address metabolic stability.
Copyright © 2016 Elsevier Ltd. All rights reserved.

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