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연구내용

1. Development of cancer-specific promoter for oncolytic adenovirus : Through the development of cancer-specific promoter that recognizes proteins overexpressed in tumor cells, the replication and cytopathic effect of oncolytic adenovirus can occur in cancer-specific manner.

2. Development of gene therapeutic that can overcome barriers of tumor microenvironment : By inserting tumor extracellular matrix degrading protein (decorin or relaxin) as therapeutic gene in an oncolytic adenovirus, an oncolytic adenovirus can selectively degrade tumor extracellular matrix and amends hypoxic conditions of tumor microenvironment, ultimately resulting in chemosenstization of tumor tissues (Int J Cancer. 2018 Jan 15;142(2):392-413, J Natl Cancer Inst. 2006 Oct 18;98(20):1482-93.)

3. Anti-angiogenesis via siRNA, zinc finger protein, or decoy receptor-based platform : By inserting antiangiogenic siRNA, zing finger protein, or decoy receptor as therapeutic gene, an oncolytic adenovirus can prevent neovasculogenesis and promote cancer cell death (Oncotarget. 2015 Feb; 6(6): 4051–4065.)

4. Development of immune gene therapeutic that can selectively express antitumor cytokines in tumor tissues : By inserting antitumor cytokines or other immunostimulatory genes as therapeutic genes, an oncolytic adenovirus can selectively express these cytokines at a high level in tumor tissues through viral replication and secondary infection (Mol Ther. 2011 Aug;19(8):1558-68., J Radiat Res. 2011;52(5):646-54.)

5. Development of nanomaterial-based oncolytic adenovirus delivery system : Oncolytic adenovirus cannot be administered systemically due to its high immunogenicity. Even if oncolytic adenovirus is highly efficacious via local administration, clinical translation of any therapeutic requires potential to treat distant metastases. By masking the surface of immunogenic viral capsid with nanomaterials, immunogenicity and other side effects commonly associated with systemically administered oncolytic viruses can be overcome.

6. Development of nanomaterial-based oncolytic adenovirus and chemotherapeutic dual delivery system : Through the development of chemotherapeutic-conjugated nanomaterial, a polyplex containing oncolytic adenovirus and chemotherapeutic can concomitantly deliver both therapeutics to tumor tissues. As these therapeutics elicit antitumor effect through different mechanisms, a synergistic anticancer effect can be achieved (Biomaterials. 2017 Nov;145:207-222.)

7. Development of tumor-targeting nanomaterial-based oncolytic adenovirus delivery system : Conjugation of nanomaterial with therapeutic antibodies targeting surface molecules preferentially overexpressed on tumor cells allows the nanomaterial to effectively target tumor cells via active targeting mechanism. This method could overcome previously identified limitations associated with passive targeting approaches. Oncolytic adenovirus complexed with tumor-targeting nanomaterial can preferentially deliver oncolytic virus to tumor tissues via systemic injection (J Control Release. 2016 Jun 10;231:2-16.)

8. Development of combination therapy regimen utilizing dendritic cells : An oncolytic adenovirus expressing set of cytokines optimized for dendritic cell activation and maturation has been developed. This oncolytic adenovirus in combination with dendritic cells overcomes immunosuppression induced by tumors to elicit potent antitumor immune response (J Control Release. 2017 Aug 10;259:115-127.)

9. Development of in vivo imaging system that can monitor therapeutic gene expression : Adenovirus expressing reporter genes (such as Green fluorescence protein, luciferase etc.) allows adenovirus activity and therapeutic gene expression to be monitored in real-time in vivo (Biomaterials 65 (2015) 163-174).

10. Clinical development of gene therapy: Evaluation of safety profile and efficacy of gene therapeutics : An oncolytic adenovirus developed by our team, DWP418, has been evaluated in phase 1 clinical trial for the treatment of patients with solid tumors that were not responding to standard therapy regimen .

11. Development of combination therapy regimen utilizing immune checkpoint inhibitors : Immune checkpoint inhibitors can disable cancer cells ability to evade host immune recognition and ultimately promotes the activation of tumor-specific T cells. By combining immune checkpoint inhibitors with immunostimulatory oncolytic adenovirus, we aim to overcome tumor-induced immunosuppression and elicit synergistic antitumor immune response

Lab members

Advisor Dr.Chae-Ok Yun

Research Professor Dr.A-rum Yoon, Dr.Kasala Dayananda, Dr.In-Wook Kim

Ph. D candidate Eonju Oh, Hyo Min Ahn, Bokyeong Jung, SooHwan Lee

M. S. candidate Jinwoo hong, Ha-Neul Ji, Tae-Geuk Kim, Yong-Hyeon Choi, Hearyung Kim, Hong Sik Kim, KyungSub Shin, Hyemin Jeong