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Optimal culture conditions for the generation of natural killer cell-induced dendritic cells for cancer immunotherapy

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Cellular & Molecular Immunology 2012年第1期9卷 45-53页

作者： Thanh-Nhan Nguyen-Pham Deok-Hwan Yang Truc-Anh Thi Nguyen Mi-Seon Lim Cheol Yi Hong Mi-Hyun Kim Hyun Ju Lee Youn-Kyung Lee Duck Cho Soo-Young Bae Jae-Sook Ahn Yeo-Kyeoung Kim Ik-Joo Chung Hyeoung-Joon Kim Je-Jung Lee Research Center for Cancer immunotherapy Chonnam National University Hwasun HospitalJeollanamdoKorea Department of Hematology-Oncology Chonnam National University Hwasun HospitalJeollanamdoKorea Vaxcell-Bio therapeutics JeollanamdoKorea The Brain Korea 21 Project Center for Biomedical Human Resources at Chonnam National UniversityGwangjuKorea

Dendritic cell(DC)-based vaccines continue to be considered an attractive tool for cancer *** require an additional signal from the environment or other immune cells to polarize the development of immune responses toward T helper 1(Th1)or Th2 *** play a role in natural killer(NK)cell activation,and NK cells are also able to activate and induce the maturation of *** investigated the types of NK cells that can induce the maturation and enhanced function of DCs and the conditions under which these interactions *** that were activated by resting NK cells in the presence of inflammatory cytokines exhibited increased expression of several costimulatory molecules and an enhanced ability to produce *** cell-stimulated DCs potently induced Th1 polarization and exhibited the ability to generate tumor antigen-specific cytotoxic T lymphocyte *** data demonstrate that functional DCs can be generated by coculturing immature DCs with freshly isolated resting NK cells in the presence of Toll-like receptor agonists and proinflammatory cytokines and that the resulting DCs effectively present antigens to induce tumor-specific T-cell responses,which suggests that these cells may be useful for cancer immunotherapy.

关键词： cancer immunotherapy dendritic cells natural killer cells signal

Immune checkpoint and inflammation as therapeutic targets in pancreatic carcinoma

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World Journal of Gastroenterology 2016年第33期22卷 7440-7452页

作者： Shiro Kimbara Shunsuke Kondo Department of Experimental therapeutics National Cancer Center Hospital

Pancreatic adenocarcinoma(PAC) is one of the most deadly malignant neoplasms,and the efficacy of conventional cytotoxic chemotherapy is far from satisfactory. Recent research studies have revealed that immunosuppression and inflammation are associated with oncogenesis,as well as tumor development,invasion,and metastasis in PAC. Thus,immunosuppressionrelated signaling,especially that involving immune checkpoint and inflammation,has emerged as novel treatment targets for PAC. However,PAC is an immuneresistant tumor,and it is still unclear whether immune checkpoint or anti-inflammation therapies would be an ideal strategy. In this article,we will review immune checkpoint and inflammation as potential targets,as well as clinical trials and the prospects for immunotherapy in PAC.

关键词： Immune checkpoint Therapeutic anticancer target Inflammation Randomized clinical trial Pancreatic adenocarcinoma

Type I and II interferons enhance dendritic cell maturation and migration capacity by regulating CD38 and CD74 that have synergistic effects with TLR agonists

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Cellular & Molecular Immunology 2011年第4期8卷 341-347页

作者： Thanh-Nhan Nguyen-Pham Mi-Seon Lim Truc Anh Thi Nguyen Youn-Kyung Lee Chun-Ji Jin Hyun Ju Lee Cheol Yi Hong Jae-Sook Ahn Deok-Hwan Yang Yeo-Kyeoung Kim Ik-Joo Chung Byoung Chul Park Hyeoung-Joon Kim Je-Jung Lee Research Center for Cancer immunotherapy Chonnam National University Hwasun HospitalJeollanamdoKorea Department of Hematology-Oncology Chonnam National UniversityGwangjuKorea The Brain Korea 21 Project Center for Biomedical Human Resources at Chonnam National UniversityGwangjuKorea Vaxcell-Bio therapeutics JeollanamdoKorea Korea Research Institute of Bioscience and Biotechnology(KRIBB) DaejeonKorea

The major limitation for the maturation of dendritic cells(DCs)using Toll-like receptor(TLR)agonists is their decreased ability to migrate into lymph nodes compared with conventional ***38 can be used as a multifunctional marker to modulate migration,survival and Th1 responses of ***74 has been shown to negatively regulate DC *** goal of this study was to investigate the combinations of TLR agonists and interferons(IFNs)that most effectively regulate CD38 and CD74 expression on *** TLR agonist stimulation in combination with IFN-a and IFN-c was the best method for regulating CD38 and CD74 expression and inducing the highest secretion of *** in vitro migration assay showed that DCs treated with this combination had significantly enhanced migratory ability,similar to that observed in cells expressing CD38,CD74 and *** results of this study suggest that an alternative maturation protocol in which two TLR ligands are combined with type I and II IFNs generates potent DCs that have both a high migratory capacity and high IL-12p70 production.

关键词： CD38 CD74 dendritic cells interferon Toll-like receptor

Prosaposin hyperglycosylation: a novel tumor immune escape mechanism and implications for cancer immunotherapy

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3150-3152页

作者： Matthias Peipp Diana Dudziak Christian Kellner Division of Antibody-Based immunotherapy Department of Medicine IChristian-Albrechts University and University Hospital Schleswig-HolsteinKielGermany institute of Immunology Jena University HospitalFriedrich-Schiller-UniversityJenaGermany Comprehensive Cancer Center Central Germany Jena/Leipzig JenaGermany Division of Transfusion Medicine Cell Therapeutics and HaemostaseologyLMU University HospitalLMU MunichMunichGermany

In a recent article published in Science,Sharma et *** the essential role of saposins in cross-presentation of tumor membraneassociated antigens by dendritic cells(DC)to CD8^(+)T cells.1 However,antigen cross-presentation,which is fundamental in cancer cell elimination,is hindered in tumor DC by hyperglycosylation of the common saposin precursor prosaposin(pSAP)leading to impaired T cell tumor immunity-yet,the potential of recombinant pSAP to re-establish T cell responses may offer a novel way to counteract immune evasion in a therapeutic approach.

关键词： impaired immunity

The delivery of effective therapeutic cancer vaccination

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Asian Journal of Andrology 2011年第2期13卷 183-184页

作者： Derek Hart Dendritic Cell Biology and therapeutics ANZACResearch Institute Sydney NSW 2139 Australia

The recent New England Journal of Medicine article describing the Phase3 placebo controlled trial （immunotherapy for Prostate Andenocarcinoma Treatment） was much anticipated. Its publication and peer review brings down the curtain on the, at times controversial, application by Dendreon to the US Food and Drug Administration. The immunotherapy for Prostate Andenocarcinoma Treatment data lead to the US Food and Drug Administration＇s final approval in April of the product sipuleucel-T （Provenge） as the first therapeutic vaccine for use in individuals with asymptomatic or minimally symptomatic hormone refractory metastatic prostate cancer.

关键词： Prostate immunotherapy Drugs Immunity Vaccines Vaccination Administration Managers Cancer (genus) Uses

Identification of novel HLA-A 0201-restricted epitopes from anterior gradient-2 as a tumor-associated antigen against colorectal cancer

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Cellular & Molecular Immunology 2012年第2期9卷 175-183页

作者： Hyun Ju Lee Cheol Yi Hong Chun-Ji Jin Mi-Hyun Kim Youn-Kyung Lee Thanh-Nhan Nguyen-Pham Hyunah Lee Byoung Chul Park Ik-Joo Chung Hyeoung-Joon Kim Je-Jung Lee Research Center for Cancer immunotherapy Chonnam National University Hwasun Hospital Hwasun Jeollanamdo Korea Department of Hematology-Oncology Chonnam National University Gwangju Korea VaxcelI-Bio therapeutics Hwasun Jeollanamdo Korea Samsung Medical Center Sungkyunkwan University School of Medicine Seoul Korea Korea Research Institute of Bioscience and Biotechnology （KRIBB） Daejeon Korea The Brain Korea 21 Project Center for Biomedical Human Resources at Chonnam National University Gwangiu Korea

Anterior gradient-2 （AGR2） promotes tumor growth, cell migration and cellular transformation and its enhanced expression is almost completely restricted to malignant tissues, thus making AGR2 an interesting target for the development of immunotherapeutic strategies. We investigated whether the AGR2 molecule comprises human leukocyte antigen （HLA）-A 0201-binding epitopes recognized by human cytotoxic T lymphocytes （CTLs）, which could be targeted in dendritic cell （DC）-based cancer immunotherapy against colorectal cancer （CRC）. We reviewed the sequence of AGR2 for peptides that could potentially bind to HLA-A 0201 with the aid of a computer-based program. Five candidate peptides with different binding scores were synthesized and tested. These peptides were then assessed for their immunogenicity to elicit specific immune responses mediated by CTLs in vitro by means of enzyme-linked immunospot assays and CTL assays. AGR2 was highly expressed in several CRC cell lines, including DK01, DLD1, KM 12C, HCT-8 and HT-29. DCs pulsed with AGR2-P2 （aa 11-19; LLVALSYTL） or AGR2-P4 （aa 127-135; RIMFVDPSL） generated potent CTLs that could lyse T2 cells pulsed with AGR2-P2 or AGR2-P4 and HLA-A0201＋ AGR2-positive CRC cell lines in a strong dose-dependent and HLA-A 0201-restricted manner. In conclusion, these novel epitopes derived from AGR2 protein may be attractive candidates for DC-based immunotherapy for CRC.

关键词： AGR2 colorectal cancer dendritic cell tumor-associated antigen

RNA binding protein TIAR modulates HBV replication by tipping the balance of pgRNA translation

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Signal Transduction and Targeted Therapy 2023年第10期8卷 4889-4902页

作者： Ting Zhang Huiling Zheng Danjuan Lu Guiwen Guan Deyao Li Jing Zhang Shuhong Liu Jingmin Zhao Ju-Tao Guo Fengmin Lu Xiangmei Chen Department of Microbiology and Infectious Disease Center School of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China Department of Pathology and Hepatology The Ffth Medical Center of Chinese PLA General HospitalBeijing 100039China Department of Experimental therapeutics Baruch S.Blumberg InstituteDoylestownPA 18902USA Bejing Key Laboratory of Hepatitis C and immunotherapy for Liver Diseases Peking University Hepatology InstitutePeking University People's HospitalBeijing 100044China

The pregenomic RNA(pgRNA)of hepatitis B virus(HBV)serves not only as a bicistronic message RNA to translate core protein(Cp)and DNA polymerase(Pol),but also as the template for reverse transcriptional replication of viral DNA upon packaging into *** it is well known that pgRNA translates much more Cp than Pol,the molecular mechanism underlying the regulation of Cp and Pol translation efficiency from pgRNA remains elusive.

关键词： translate template translation

An mRNA vaccine elicits STING-dependent antitumor immune responses

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Acta Pharmaceutica Sinica B 2023年第3期13卷 1274-1286页

作者： Zhe Chen Chaoyang Meng Junhua Mai Yongbin Liu Hangwen Li Haifa Shen Department of Nanomedicine Houston Methodist Academic InstituteHoustonTX 77030USA Xiangya Hospital of Central South University Changsha 410000China Department of Hepatobiliary and Pancreatic Surgery First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Stemirna therapeutics Shanghai 201206China ImmunoQ therapeutics HoustonTX 77401USA

Lipid-formulated RNA vaccines have been widely used for disease prevention and treatment,yet their mechanism of action and individual components contributing to such actions remain to be ***,we show that a therapeutic cancer vaccine composed of a protamine/mRNA core and a lipid shell is highly potent in promoting cytotoxic CD8+T cell responses and mediating anti-tumor ***,both the mRNA core and lipid shell are needed to fully stimulate the expression of type I interferons and inflammatory cytokines in dendritic *** of interferon-βexpression is exclusively dependent on STING,and antitumor activity from the mRNA vaccine is significantly compromised in mice with a defective Sting ***,the mRNA vaccine elicits STING-dependent antitumor immunity.

关键词： Cancer immunotherapym RNA Vaccine Dendritic cells EDOPCS TING MAVS

Molecular therapeutics in pancreas cancer

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World Journal of Gastrointestinal Oncology 2016年第4期8卷 366-379页

作者： Vignesh Narayanan Colin D Weekes Division of Medical Oncology Department of Medicine Developmental Therapeutics Program University of Colorado Cancer Center University of Colorado School of Medicine

The emergence of the "precision-medicine" paradigm in oncology has ushered in tremendous improvements in patient outcomes in a wide variety of malignancies. However, pancreas ductal adenocarcinoma(PDAC) has remained an obstinate challenge to the oncology community and continues to be associated with a dismal prognosis with 5-year survival rates consistently less than 5%. Cytotoxic chemotherapy with gemcitabine-based regimens has been the cornerstone of treatment in PDAC especially because most patients present with inoperable disease. But in recent years remarkable basic science research has improved our understanding of the molecular and genetic basis of PDAC. Whole genomic analysis has exemplified the genetic heterogeneity of pancreas cancer and has led to ingenious efforts to target oncogenes and their downstream signaling cascades. Novel stromal depletion strategies have been devised based on our enhanced recognition of the complex architecture of the tumor stroma and the various mechanisms in the tumor microenvironment that sustain tumorigenesis. immunotherapy using vaccines and immune checkpoint inhibitors has also risen to the forefront of therapeutic strategies against PDAC. Furthermore, adoptive T cell transfer and strategies to target epigenetic regulators are being explored with enthusiasm. This review will focus on the recent advances in molecularly targeted therapies in PDAC and offer future perspectives to tackle this lethal disease.

关键词： Pancreas neoplasm Vaccines Targeted therapy immunotherapy Kirsten rat sarcoma oncogene