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Cellular immunotherapy in multiple myeloma
Manh-Cuong Vo,THANGARAJ JAYA LAKSHMI,정성훈,조덕,박혜성,Tan-Huy Chu,이현주,김형준,김상기,이제정 대한내과학회 2019 The Korean Journal of Internal Medicine Vol.34 No.5
In multiple myeloma (MM), the impaired function of several types of immune cells favors the tumor’s escape from immune surveillance and, therefore, its growth and survival. Tremendous improvements have been made in the treatment of MM over the past decade but cellular immunotherapy using dendritic cells, natural killer cells, and genetically engineered T-cells represent a new therapeutic era. The application of these treatments is growing rapidly, based on their capacity to eradicate MM. In this review, we summarize recent progress in cellular immunotherapy for MM and its future prospects.
Nguyen-Pham, Thanh-Nhan,Jung, Sung-Hoon,Vo, Manh-Cuong,Thanh-Tran, Huong-Thi,Lee, Youn-Kyung,Lee, Hyun-Ju,Choi, Nu-Ri,Hoang, My-Dung,Kim, Hyeoung-Joon,Lee, Je-Jung Lippincott-Raven 2015 Journal of immunotherapy Vol.38 No.8
We investigated the efficacy of lenalidomide (LEN) in combination with dendritic cell (DC) vaccination in the MOPC-315 murine myeloma model. After tumor growth, LEN was injected intraperitoneally for 4 consecutive days in combination with DC vaccination. The combination of LEN and vaccination efficiently inhibited tumor growth compared with the single agents alone. A cytotoxic assay revealed that the anticancer effects of DC vaccination plus LEN involved not only generation of antigen-specific cytotoxic T lymphocytes but also NK cells. Vaccinated mice had reduced numbers of suppressor cells, including both myeloid-derived suppressor cells and regulatory T cells, in the spleen. The proportions of CD4 and CD8 T cells increased in the spleen, and a Th1 cytokine (interferon-&ggr;) rather than a Th2 cytokine (interleukin-10) was synthesized in response to tumor antigens. LEN enhanced the innate immune response by modulating NK cell numbers and function. In addition, LEN reduced the production levels of angiogenesis-inducing factors in tumor-bearing mice. Together, these results suggest that a combination of LEN and DC vaccination may synergistically enhance anticancer immunity in the murine myeloma model, by inhibiting immunosuppressor cells and stimulating effector cells, as well as effectively polarizing the Th1/Th2 balance in favor of a Th1-specific immune response.
Van-Truc Nguyen,Thanh-Binh Nguyen,Thi-Dieu-Hien Vo,Nguyen Duy Dat,Thi-Kim Quyen Vo,Xuan Cuong Nguyen,Viet-Cuong Dinh,Thi-Ngoc-Chau Le,Thi-Giang-Huong Duong,Manh-Ha Bui,Xuan-Thanh Bui 대한환경공학회 2023 Environmental Engineering Research Vol.29 No.3
This study explores the adsorption of doxycycline (DOX) from aqueous solutions onto biochar derived from banana peel, which was prepared using a potassium hydroxide activation method (KOH-BPB). The biochar properties were characterized based on morphology, surface area (SBET of 710.241 ㎡ g<SUP>−1</SUP>), functional groups, and surface charge (pHPZC = 7.7). Parameters, including initial pH, DOX concentration, and ionic strength, that influenced the DOX adsorption capacity of KOH-BPB were examined. Adsorption equilibrium of DOX on KOH-BPB was assessed through four isothermal models: the Langmuir, Freundlich, Temkin, and Dubinin-Radushkevich models. The obtained data were most compatible with the Langmuir model (R² = 0.9879). KOH-BPB has a maximum DOX absorption capacity of 121.95 mg g<SUP>-1</SUP> which exceeds that of many comparable absorbents. The maximum DOX removal was 96.7% at pH 6, a DOX concentration of 20 mg L<SUP>-1</SUP>, and a KOH-BPB dose of 1.0g L<SUP>-1</SUP>. These findings reveal that biochar from banana peel effectively removes antibiotic residues from water. This study provides a potential, low-cost, and environmentally friendly adsorbent.
Dendritic Cell-Based Cancer Immunotherapy against Multiple Myeloma: From Bench to Clinic
My-Dung Hoang,정성훈,이현주,이연경,이연경,Thanh Nhan Nguyen Pham,최누리,Manh-Cuong Vo,이승신,안재숙,양덕환,김여경,김형준,이제중 전남대학교 의과학연구소 2015 전남의대학술지 Vol.51 No.1
Although the introduction of stem cell transplantation and novel agents has improvedsurvival, multiple myeloma (MM) is still difficult to cure. Alternative approaches areclearly needed to prolong the survival of patients with MM. Dendritic cell (DC) therapyis a very promising tool immunologically in MM. We developed a method to generatepotent DCs with increased Th1 polarization and migration ability for inducing strongmyeloma-specific cytotoxic T lymphocytes. In this review, we discuss how the efficacyof cancer immunotherapy using DCs can be improved in MM.
Choi, Nu-Ri,Lee, Hyun-Ju,Jung, Sung-Hoon,Hong, Cheol Yi,Vo, Manh-Cuong,Hoang, My-Dung,Kim, Hyeoung-Joon,Lee, Je-Jung Elsevier 2015 cytotherapy Vol.17 No.10
<P>Background aims. It is important to improve the migratory ability of dendritic cells (DCs) and to increase DC potency for successful DC-based cancer immunotherapy. The intracellular Ca2+ signaling pathway has an important role on the regulation of DC migration. Our preliminary studies revealed that sarco/endoplasmic reticulum Ca2+ transport ATPase 2 (SERCA2) expression was inversely related to DC migratory capacity, and the expression level of p-cofilin and SERCA2 on mature DCs showed a counter-trend. Methods. We selected the appropriate six maturation cocktails on the basis of the expression levels of SERCA2 and p-cofilin and investigated the functional characteristics and migratory capacity of mature DCs. Among the these six maturation cocktails, DCIFN-gamma/IL-I beta/Poly-I:C showed potent type 1 immune response with interleukin (IL)-12p70 production and strong Th1-polarization, and this DC elicited strong antigen-specific cytotoxic Tlymphocyte responses. Results. Interestingly, DCIFN-gamma/IL-I beta/Poly-I:C showed lower expression of SERCA2 and higher expression of p-cofilin compared with those matured with the use of other cocktails. In vitro migration assay showed that DCs matured with the use of this maturation cocktail had significantly increased migratory ability compared with alpha DC1s and other DCs. Conclusions. Interferon-gamma, IL-1 beta and Poly-I:C maturation cocktail may be used in the field of cancer immunotherapy to generate potent immune-stimulatory DCs with improved type 1 immune response and migration capacity.</P>
Cheol Yi Hong,이현주,Nu-Ri Choi,정성훈,Manh-Cuong Vo,My-Dung Hoang,김형준,이제중 생화학분자생물학회 2016 Experimental and molecular medicine Vol.48 No.-
The migration of dendritic cells (DCs) to secondary lymphoid organs depends on chemoattraction through the interaction of the chemokine receptors with chemokines. However, the mechanism of how lymphoid chemokines attract DCs to lymphoid organs remains unclear. Here, we demonstrate the mechanism of DC migration in response to the lymphoid chemokine CCL21. CCL21-mediated DC migration is controlled by the regulation of sarcoplasmic reticulum Ca2+ ATPase 2 (SERCA2) expression rather than through the activation of mitogen-activated protein kinases CCL21-exposed mature DCs (mDCs) exhibited decreased SERCA2 expression but not decreased phospholamban (PLB) or Hax-1 expression, which are known to be SERCA2-interacting proteins. In addition, CCL21 did not affect the mRNA levels of SERCA2 or its interacting protein Hax-1. Interestingly, SERCA2 expression was inversely related to DC migration in response to chemokine stimulation. The migratory capacity of CCL21-treated mDCs was decreased by the phospholipase C inhibitor U73122 and by the protein kinase C inhibitor BAPTA-AM. The migratory capacities of mDCs were increased in response to SERCA2 siRNA expression but were decreased by SERCA2 overexpression. In addition, DCs treated with a SERCA2-specific inhibitor (cyclopiazonic acid) had significantly increased migratory capacities as mDCs regardless of SERCA2 expression. Moreover, SERCA2 expression was dependent on DC maturation induced by cytokines or Toll-like receptor agonists. Therefore, the migratory capacities differed in differentially matured DCs. Taken together, these results suggest that SERCA2 contributes to the migration of CCL21-activated DCs as an important feature of the adaptive immune response and provide novel insights regarding the role of SERCA2 in DC functions.
Dendritic Cell-Based Cancer Immunotherapy against Multiple Myeloma: From Bench to Clinic
Hoang, My-Dung,Jung, Sung-Hoon,Lee, Hyun-Ju,Lee, Youn-Kyung,Nguyen-Pham, Thanh-Nhan,Choi, Nu-Ri,Vo, Manh-Cuong,Lee, Seung-Shin,Ahn, Jae-Sook,Yang, Deok-Hwan,Kim, Yeo-Kyeoung,Kim, Hyeoung-Joon,Lee, Je- Chonnam National University Medical School 2015 CMJ Vol.51 No.1
<P>Although the introduction of stem cell transplantation and novel agents has improved survival, multiple myeloma (MM) is still difficult to cure. Alternative approaches are clearly needed to prolong the survival of patients with MM. Dendritic cell (DC) therapy is a very promising tool immunologically in MM. We developed a method to generate potent DCs with increased Th1 polarization and migration ability for inducing strong myeloma-specific cytotoxic T lymphocytes. In this review, we discuss how the efficacy of cancer immunotherapy using DCs can be improved in MM.</P>