• 대한의생명과학회지
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• 제25권3호
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• pp.201-210
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• 2019

The oncolytic viruses selectively infect and destroy cancer cells, not harming normal cells. The cancer cell materials released by oncolysis, like tumor antigens, stimulate host antitumor immune responses, which is a long-lasting antitumor immunity removing cancer cells in remote parts of the body by a systemic response. Oncolytic viruses armed with transgenes such as cytokines or other immune stimulating factors enhance the immune responses. The first oncolytic virus approved by US-FDA is $Imlygic^{(R)}$ targeting for melanoma. The oncolytic virus is considered as a revolutionary immunotherapy for tumors together with immune checkpoint inhibitors. A variety of oncolytic viruses are under research in the treatment of kidney cancer, liver cancer, breast cancer, and many others solid tumors. Clinical trials have shown promising results in different types of cancers. Here, we present a brief introduction of various aspects of oncolytic virus, and a review of the current status of oncolytic virus therapy development.

• International journal of advanced smart convergence
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• 제9권1호
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• pp.90-97
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• 2020

Oncolytic viruses are characterized by their ability to selectively kill cancer cells, and thus they have potential for application as novel anticancer agents. Despite an increase in the number of studies on methodologies involving oncolytic viruses, bioinformatic studies generating useful data are lacking. We constructed a database for oncolytic virus research (the oncolytic virus database, OVDB) by integrating scattered genetic information on oncolytic viruses and proposed a systematic means of using the biological data in the database. Our database provides data on 14 oncolytic viral strains and other types of viruses for comparative analysis. We constructed the OVDB using the basic local alignment search tool, and therefore can provides genetic information on highly homologous oncolytic viruses. This study contributes to facilitate systematic bioinformatics research, providing valuable data for development of oncolytic virus-based anticancer therapies.

• 대한의생명과학회지
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• 제19권4호
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• pp.303-309
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• 2013

Oncolytic vaccinia virus is an engineered vaccinia virus that selectively destroys cancer cells and induces tumor immune response. Oncolytic vaccinia expressing mouse GM-CSF showed cytotoxic activity against various kinds of cancer cells when oncolytic vaccinia virus expressing human GM-CSF and mouse GM-CSF is intravenously administered in the mouse CT26 colon tumor model. Cancer cells treated with isolated immunoglobulin G from the serum with complement showed these cytotoxic activity and complement observed dose-dependent cytotoxic effect. These results suggest that oncolytic vaccinia virus expressing mouse GM-CSF can increase oncolytic vaccinia virus by inducing anticancer antibody in a mouse tumor model. Further studies are needed on antitumor immunity of GM-CSF.

• 대한의생명과학회지
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• 제18권3호
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• pp.210-217
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• 2012

Oncolytic viral vectors have shown good candidates for cancer treatment but have many limitations. To improve the therapeutic potential of oncolytic vaccinia virus, we developed a recombinant vaccinia virus expressing the 4-1BBL co-stimulatory molecule or CCL21. 4-1BBL and CCL21 expression was identified by FACS analysis and immunoblotting. rV-4-1BBL vaccination shows significant tumor regression compared to rV-LacZ, but rV-CCL21 shows rapid tumor growth compared to rV-LacZ in the poorly immunogenic B16 murine melanoma model. 4-1BBL expression resulted in the increase of the number of CD8+ T cells and especially the increase of effector (CD62L-CD44+) CD8+ T cells. These data suggest 4-1BBL may be the potential target for enhancement of tumor immunotherapy.

• BMB Reports
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• 제48권10호
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• pp.565-570
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• 2015

In several reports, the respiratory syncytial virus (RSV) was identified as an oncolytic virus in cancer cells (e.g., lung and prostate cancer). However, the effects of RSV in hepatocellular carcinoma (HCC) cells have not yet been investigated. Here, we observed the inhibitory effects of RSV infection in HCC cell-lines. Cell growth was significantly decreased by RSV infection in BNL-HCC, Hep3B, Huh-7 and SNU-739 cells. After RSV infection, plaque formation and syncytial formation were observed in affected Hep3B and Huh-7 cells. RSV protein-expression was also detected in Hep3B and Huh-7 cells; however, only Huh-7 cells showed apoptosis after RSV infection. Furthermore, inhibition of cell migration by RSV infection was observed in BNL-HCC, Hep3B, Huh-7 and SNU-739 cells. Therefore, further investigation is required to clarify the molecular mechanism of RSV-mediated inhibition of HCC cell growth, and to develop potential RSV oncolytic viro-therapeutics.

• 대한임상약리학회:학술대회논문집
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• 대한임상약리학회 2006년도 제15차 추계학술대회
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• pp.29-30
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• 2006

• 생명과학회지
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• 제29권7호
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• pp.824-835
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• 2019

최근 수십 년 간 종양 용해성 바이러스(Oncolytic viruses; OV)는 암 치료제로서의 잠재성에 의해 광범위하게 연구되어왔다. 종양 용해성 바이러스는 두 가지의 독특한 장점을 가지고 있는데, 첫째로 암세포만을 특이적으로 감염시키고 사멸시킬 수 있다는 것이고, 두 번째로는 암이 진행되는 초기 단계에 숨어서 인식되지 않는 상태인 종양 관련 항원들을 인식하는 특정한 적응 면역을 활성화 시키는 것이다. 2015년에는 유전자 변형 종양 용해성 바이러스인 Talminogene laherparepvec (T-VEC)이 미국 식약청(FDA)의 승인을 받았으며, 현재는 다양한 종양 용해성 바이러스들이 단일로 사용되거나 기존의 암 치료 방법인 면역 치료법, 방사선 치료법, 화학 치료법과 함께 사용되어 임상 시험에서 활성이 연구되고 있다. 종양 용해성 바이러스 치료법의 효능은 항 종양 면역 활성과 항바이러스 반응의 균형이 어느 정도인가에 의해 조절되기 때문에, 획기적인 성과에도 불구하고 암 치료를 위한 종양 용해성 바이러스의 개발은 전달 방법, 바이러스를 인식하는 신체 내 항체 및 종양의 복잡성, 가변성, 반응성에 따른 항바이러스의 면역 유도와 같은 다양한 장애물을 극복하여야 하는 문제가 있다. 종양 내에 직접 종양 용해성 바이러스를 투여하는 방법은 눈에 띄는 부작용이 없이 고형 종양을 줄이는 것에 성공하였으나, 아쉽게도 뇌종양 같은 일부 종양에는 사용할 수 없고 전신 투여가 필요한 단점이 존재한다. 이러한 장애물들을 극복하기 위해서 종양 용해성 바이러스의 효능을 높이기 위한 형질 전환 유전자의 삽입 혹은 면역 조절 물질과 바이러스를 조합하는 등의 다양한 전략들이 개발되고 있다.

• BMB Reports
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• 제36권4호
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• pp.379-386
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• 2003

A mutant herpes simplex virus 1, mtHSV, was constructed by inserting the E. coli beta-galactosidase gene into the loci of icp34.5, the apoptosis-inhibiting gene of HSV. The mtHSV replicated in and lysed U251 (human glioma cells), EJ (human bladder cells), and S-180 (mice sarcoma cells), but not Wish (human amnion cells) cells. With its intact tk (thymidine kinase) gene, mtHSV exhibited susceptibility to acyclovir (ACV), which provided an approach to control viral replication. An in vivo test with mtHSV was conducted in immune-competent mice bearing sarcoma S-180 tumors, which were treated with a single intratumoral injection of mtHSV or PBS. Tumor dimensions then were measured at serial time points, and the tumor volumes were calculated. Sarcoma growth was significantly inhibited with prolonged time and reduced tumor volume. There was microscopic evidence of necrosis of tumors in treated mice, whereas no damage was found in other organs. Immunohistochemical staining revealed that virus replication was exclusively confined to the treated tumor cells. HSV-1 DNA was detected in tumors, but not in the other organs by a polymerase chain reaction analysis. From these experiments, we concluded that mtHSV should be a safe and promising oncolytic agent for cancer treatment.

• 대한의생명과학회지
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• 제17권3호
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• pp.185-190
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• 2011

Adenovirus type 5 (Ad5) vectors have been used for gene transfer to a wide variety of cell types in vivo and in vitro. The advantages of adenovirus vectors include the high titer of virus readily obtained in large scale preparations, their ability to transduce dividing and non dividing cells, and the high level of transgene expression. Since adenovirus vectors do not integrate in host cell DNA, there is a lack of insertional mutagenesis. However, many human tumor cells lack expression of the adenovirus 5 receptors and contain areas of hypoxia. In order to identify the pattern of replication and gene expression of oncolytic adenovirus in hypoxic condition, multiple different fiber modified Ads (Ad5F/S11, Ad5F/S35, Ad5F/K7, Ad5F/K21, and Ad5F/RGD) was compared. The replication of all fiber modified adenovirus was inhibited in hypoxic condition in HEK 293 cells, but gene expression has variety on different tumor cell lines and the level of coxackievirus and adenovirus receptor (CAR) expression. These data suggest that CAR expression pattern and hypoxic condition of tumor are considered for optimal oncolytic adenovirus application.

• BMB Reports
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• 제48권8호
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• pp.454-460
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• 2015

Naturally occurring reoviruses are live replication-proficient viruses that specifically infect human cancer cells while sparing their normal counterpart. Since the discovery of reoviruses in 1950s, they have shown various degrees of safety and efficacy in pre-clinical or clinical applications for human anti-cancer therapeutics. I have recently discovered that cellular tumor suppressor genes are also important in determining reoviral tropism. Carcinogenesis is a multi-step process involving the accumulation of both oncogene and tumor suppressor gene abnormalities. Reoviruses can exploit abnormal cellular tumor suppressor signaling for their oncolytic specificity and efficacy. Many tumor suppressor genes such as p53, ataxia telangiectasia mutated (ATM), and retinoblastoma associated (RB) are known to play important roles in genomic fidelity/maintenance. Thus, a tumor suppressor gene abnormality could affect host genomic integrity and likely disrupt intact antiviral networks due to the accumulation of genetic defects which in turn could result in oncolytic reovirus susceptibility. This review outlines the discovery of oncolytic reovirus strains, recent progresses in elucidating the molecular connection between oncogene/tumor suppressor gene abnormalities and reoviral oncotropism, and their clinical implications. Future directions in the utility of reovirus virotherapy is also proposed in this review. [BMB Reports 2015; 48(8): 454-460]