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Assessment of therapeutic efficacy mediated by oncolytic Ad co-expressing IL-12 and decorin in combination with NK cells

Title
Assessment of therapeutic efficacy mediated by oncolytic Ad co-expressing IL-12 and decorin in combination with NK cells
Other Titles
IL-12와 decorin을 동시에 발현하는 종양 선택적 살상 아데노바이러스와 자연살상세포의 병합투여에 의한 향상된 항종양 효과 평가
Author
염춘영
Alternative Author(s)
Lian, ChunYing
Advisor(s)
윤채옥
Issue Date
2017-08
Publisher
한양대학교
Degree
Master
Abstract
Recently, natural killer (NK) cell therapy is a promising approach in treating cancer. However, clinical trials have indicated that immunosuppressive tumor milieu suppress antitumor immune response and inhibit cytotoxic activity of NK cells, resulting in inadequate reduction of tumor burdens. To overcome these limitations and enhance the efficiency of NK cell therapy, combination of NK cells with immune stimulatory oncolytic adenovirus (Ad) have been explored. Oncolytic Ad (RdB/IL-12/DCN) co-expresses interleukin (IL)-12 and decorin (DCN) plus NK cells (either human or murine NK cells) elicited potent anticancer effect by superior induction of apoptosis. RdB/IL-12/DCN plus human NK cells attenuated immunosuppressive myeloid-derived suppressor cells (MDSC) population level, leading to potent antitumor efficacy in H460 subcutaneous xenograft model and A549 orthotopic lung cancer model. Moreover, RdB/IL-12/DCN in combination with human NK cells showed significantly enhanced necrosis and inhibition tumor cell proliferation than either oncolytic Ad or NK cell alone. Taken together, oncolytic Ad co-expressing IL-12 and DCN can ameliorate immunosuppressive tumor microenvironment and enhance cytotoxicity of NK cell, making it a promising strategy to overcome current limitations of NK cell in clinical trial.
URI
http://hdl.handle.net/20.500.11754/33394http://hanyang.dcollection.net/common/orgView/200000430869
Appears in Collections:
GRADUATE SCHOOL[S](대학원) > BIOENGINEERING(생명공학과) > Theses (Ph.D.)
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