EDITOR’S CHOICE – Oncolytic Tanapoxvirus Expressing Interleukin-2 is Capable of Inducing the Regression of Human Melanoma Tumors in the Absence of T Cells

Journal: Current Cancer Drug Targets

Author(s): Tiantian Zhang, Dennis H. Kordish, Yogesh R. Suryawanshi, Rob R. Eversole, Steven Kohler,Charles D. Mackenzie, Karim Essani*.

Graphical Abstract:

 

Abstract:

Background: Oncolytic viruses (OVs), which preferentially infect cancer cells and induce host anti-tumor immune responses, have emerged as an effective melanoma therapy. Tanapoxvirus (TANV), which possesses a large genome and causes mild self-limiting disease in humans, is potentially an ideal OV candidate. Interleukin-2 (IL-2), a T-cell growth factor, plays a critical role in activating T cells, natural killer (NK) cells and macrophages in both the innate and adaptive immune system.

Objective: We aimed to develop a recombinant TANV expressing mouse IL-2 (TANVΔ66R/mIL- 2), replacing the viral thymidine kinase (TK) gene (66R) with the mouse (m) mIL-2 transgene resulting in TANVΔ66R/mIL-2.

Methods: Human melanoma tumors were induced in female athymic nude mice by injecting SKMEL- 3 cells subcutaneously. Mice were treated with an intratumoral injection of viruses when the tumor volumes reached 45 ± 4.5 mm3.

Results: In cell culture, expression of IL-2 attenuated virus replication of not only TANVΔ66R/ mIL-2, but also TANVGFP. It was demonstrated that IL-2 inhibited virus replication through intracellular components and without activating the interferon-signaling pathway. Introduction of mIL-2 into TANV remarkably increased its anti-tumor activity, resulting in a more significant regression than with wild-type (wt) TANV and TANVΔ66R. Histopathological studies showed that extensive cell degeneration with a significantly increased peri-tumor accumulation of mononuclear cells in the tumors treated with TANVΔ66R/mIL-2, compared to wtTANV or TANVΔ66R.

Conclusion: We conclude that TANVΔ66R/mIL-2 is potentially therapeutic for human melanomas

 

Read more here: http://www.eurekaselect.com/153638/article

 

HIGHLIGHTED ARTICLE – A Therapeutic Potential of Animal β-hairpin Antimicrobial Peptides – CURRENT MEDICINAL CHEMISTRY

Cmc-Articles_24-42-Vadim T. Ivanov

To access the article, please visit: http://www.eurekaselect.com/151833/article

Testimonial by Olga Tsachouridou!

Olga Tsachouridou

Contributed Article: “Deficient Phagocytosis Among HIV-1 Infected Adults Over Time Even in HAART Setting

 

Editor’s Choice – Model Validity in Nanoimmunosafety: Advantages and Disadvantages of In vivo vs In vitro Models, and Human vs Animal Models – Current Bionanotechnology

Journal: Current Bionanotechnology

Author(s): Diana Boraschi, Paola Italiani.

Graphical Abstract:

 

Abstract:

The thorough understanding of the interaction between nanomaterials and the immune system is the starting point both for nanomaterial exploitation in nanomedicine and for the implementation of an effective regulatory framework concerning nanosafety for human health and the environment. In this context, the use of valid models, in vitro and in vivo, is central for assessing both the positive and the detrimental effects of nanomaterials, thereby predicting their possible risks for human and environmental health. Thus, predicting models are sought that allow us on one side defining hazard posed by nanomaterials, and therefore implementing safety regulation and safe-by-design nanotechnologies, and on the other side exploiting nanomaterials for more effective therapeutic and preventive medical strategies. Here, we consider the advantages and limitation of the current in vitro and in vivo human and animal models, and the appropriateness of their use for assessing the effects of nanomaterials on immunity.

Read more here: http://www.eurekaselect.com/142770

Podcast: Oncolytic Tanapoxvirus Expressing Interleukin-2 Is Capable Of Inducing The Regression Of Human Melanoma Tumors In The Absence Of T Cells by Dr. Zhang

Author(s): Tiantian Zhang, Dennis H Kordish, Yogesh R Suryawanshi, Rob R Eversole, Steven Kohler, Charles D Mackenzie, Karim Essani

For article details, visit: http://www.eurekaselect.com/153638/article

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