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https://www.readbyqxmd.com/read/28231510/lipopolyplex-potentiates-anti-tumor-immunity-of-mrna-based-vaccination
#1
Stefano Persano, Maria L Guevara, Zhaoqi Li, Junhua Mai, Mauro Ferrari, Pier Paolo Pompa, Haifa Shen
mRNA-based vaccines have the benefit of triggering robust anti-cancer immunity without the potential danger of genome integration from DNA vaccines or the limitation of antigen selection from peptide vaccines. Yet, a conventional mRNA vaccine comprising of condensed mRNA molecules in a positively charged protein core structure is not effectively internalized by the antigen-presenting cells. It cannot offer sufficient protection for mRNA molecules from degradation by plasma and tissue enzymes either. Here, we have developed a lipopolyplex mRNA vaccine that consists of a poly-(β-amino ester) polymer mRNA core encapsulated into a 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine/1,2-dioleoyl-sn-glycero-3-phosphatidyl-ethanolamine/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000 (EDOPC/DOPE/DSPE-PEG) lipid shell...
February 20, 2017: Biomaterials
https://www.readbyqxmd.com/read/28229217/foxo3-estrogen-receptor-alpha-and-androgen-receptor-impact-tumor-growth-rate-and-infiltration-of-dendritic-cell-subsets-differentially-between-male-and-female-mice
#2
Matthew G Thompson, Daniel S Peiffer, Michelle Larson, Flor Navarro, Stephanie K Watkins
Tumors evade immune recognition and destruction in many ways including the creation of an immune-suppressive tumor microenvironment (TME). Dendritic cells (DC) that infiltrate the TME are tolerogenic, and suppress effector T cells and anti-tumor activity. Previous reports demonstrated that a key regulator of tolerance in DC is the transcription factor FOXO3. Gender disparity has been studied in cancer in relation to incidence, aggressiveness, and prognosis. Few studies have touched on the importance in relation to impact on the immune system...
February 22, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28228759/interleukin-35-producing-cd8%C3%AE-dendritic-cells-acquire-a-tolerogenic-state-and-regulate-t-cell-function
#3
Sergio Haller, Anaïs Duval, Romain Migliorini, Mathias Stevanin, Vanessa Mack, Hans Acha-Orbea
Dendritic cells (DCs) play a central role in shaping immunogenic as well as tolerogenic adaptive immune responses and thereby dictate the outcome of adaptive immunity. Here, we report the generation of a CD8α(+) DC line constitutively secreting the tolerogenic cytokine interleukin (IL)-35. IL-35 secretion led to impaired CD4(+) and CD8(+) T lymphocyte proliferation and interfered with their function in vitro and also in vivo. IL-35 was furthermore found to induce a tolerogenic phenotype on CD8α(+) DCs, characterized by the upregulation of CD11b, downregulation of MHC class II, a reduced costimulatory potential as well as production of the immunomodulatory molecule IL-10...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28224211/mechanisms-overseeing-myeloid-derived-suppressor-cell-production-in-neoplastic-disease
#4
REVIEW
Colleen S Netherby, Scott I Abrams
Perturbations in myeloid cell differentiation are common in neoplasia, culminating in immature populations known as myeloid-derived suppressor cells (MDSCs). MDSCs favor tumor progression due to their ability to suppress host immunity or promote invasion and metastasis. They are thought to originate from the bone marrow as a result of exposure to stromal- or circulating tumor-derived factors (TDFs). Although great interest has been placed on understanding how MDSCs function, less is known regarding how MDSCs develop at a transcriptional level...
February 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28223815/antitumor-effects-of-oncolytic-herpes-simplex-virus-type-2-against-colorectal-cancer-in-vitro-and-in-vivo
#5
Lei Yin, Chunhong Zhao, Jixia Han, Zengjun Li, Yanan Zhen, Ruixue Xiao, Zhongfa Xu, Yanlai Sun
BACKGROUND: The incidence of colorectal cancer (CRC) is on the rise. Furthermore, late-stage diagnoses and limited efficacious treatment options make CRC a complex clinical challenge. Therefore, a new therapeutic regimen with a completely novel therapeutic mechanism is necessary for CRC. In the present study, the therapeutic efficacy of oncolytic herpes simplex virus type 2 (oHSV2) in CRC was assessed in vitro and in vivo. oHSV2 is an oncolytic agent derived from herpes simplex virus type 2 that encodes granulocyte-macrophage colony-stimulating factor...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28223726/dendritic-cells-engineered-to-secrete-anti-dcr3-antibody-augment-cytotoxic-t-lymphocyte-response-against-pancreatic-cancer-in-vitro
#6
Jiang Chen, Xiao-Zhong Guo, Hong-Yu Li, Jia-Jun Zhao, Wen-Da Xu
AIM: To investigate the enhanced cytotoxic T lymphocyte responses against pancreatic cancer (PC) in vitro induced by dendritic cells (DCs) engineered to secrete anti-DcR3 monoclonal antibody (mAb). METHODS: DCs, T lymphocytes and primary PC cells were obtained from PC patients. DCs were transfected with a designed humanized anti-DcR3 monoclonal antibody heavy and light chain mRNA and/or total tumor RNA (DC-tumor-anti-DcR3 RNA or DC-total tumor RNA) by using electroporation technology...
February 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28221800/self-associating-poly-ethylene-oxide-block-poly-%C3%AE%C2%B5-caprolactone-peo-b-pcl-drug-conjugates-for-the-delivery-of-stat3-inhibitor-jsi-124-potential-application-in-cancer-immunotherapy
#7
Shyam M Garg, Mohammad Reza Vakili, Ommoleila Molavi, Afsaneh Lavasanifar
Constitutive activation of signal transducer and activator of transcription 3 (STAT3) in tumor cells and tumor associated dendritic cells (DCs) plays a major role in the progression of cancer. JSI-124 (Cucurbitacin I) is a potent inhibitor of STAT3, however, its poor solubility and non-specificity limits its effectiveness in cancer immunotherapy. In order to achieve a nano-carrier for solubilisation and passive targeting of JSI-124 to tumor cells and tumor associated DCs, the drug was chemically conjugated to pendent COOH groups of self-associating poly(ethylene oxide)-block-poly(-carboxylate-ε-caprolactone) (PEO-b-PCCL)...
February 21, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28221292/dermatofibroma-of-the-eyelid-immunohistochemical-diagnosis
#8
Frederick A Jakobiec, Fouad R Zakka, Yufei Tu, Suzanne K Freitag
A 66-year-old man developed a painless 2 mm to 3 mm recurrent nodule at the left upper eyelid margin. Excision disclosed a spindle cell lesion without frank atypia or mitotic activity growing in a twisted fascicular pattern often referred to as storiform. All the surgical margins were involved with tumor. Immunohistochemistry demonstrated that many of the constituent spindle and dendritic tumor cells were CD34, factor XIIIa, and CD 163, the latter 2 being biomarkers for monocytic lineage. The lesion was diagnosed as a dermatofibroma rather than a fibrous histiocytoma, a term that should be reserved for more aggressive lesions of deeper fascial planes...
February 17, 2017: Ophthalmic Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28219803/maintaining-unperturbed-cerebral-blood-flow-is-key-in-the-study-of-brain-metastasis-and-its-interactions-with-stress-and-inflammatory-responses
#9
Benbenishty Amit, Segev-Amzaleg Niva, Shaashua Lee, Melamed Rivka, Ben-Eliyahu Shamgar, Blinder Pablo
Blood-borne brain metastases are associated with poor prognosis, but little is known about the interplay between cerebral blood flow, surgical stress responses, and the metastatic process. The intra-carotid inoculation approach, traditionally used in animal studies, involves permanent occlusion of the common carotid artery (CCA). Herein we introduce a novel intra-carotid inoculation approach that avoids CCA ligation, namely - assisted external carotid artery inoculation (aECAi) - and compared it to the traditional approach in C57/BL6 mice, assessing cerebral blood flow; particle distribution; blood-brain barrier (BBB) integrity; stress, inflammatory and immune responses; and tumor brain retention and growth...
February 17, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28215654/dendritic-cell-vaccination-in-combination-with-docetaxel-for-patients-with-metastatic-castration-resistant-prostate-cancer-a-randomized-phase-ii-study
#10
Per Kongsted, Troels Holz Borch, Eva Ellebaek, Trine Zeeberg Iversen, Rikke Andersen, Özcan Met, Morten Hansen, Henriette Lindberg, Lisa Sengeløv, Inge Marie Svane
BACKGROUND AIMS: We investigated whether the addition of an autologous dendritic cell-based cancer vaccine (DCvac) induces an immune response in patients with metastatic castration-resistant prostate cancer treated with docetaxel. METHODS: Forty-three patients were randomized 1:1 to receive up to 10 cycles of docetaxel alone, 75 mg/m(2) every 3 weeks or in combination with DCvac. Monocytes were harvested following a leukapheresis procedure, matured ex vivo and subsequently transfected with messenger RNA encoding multiple tumor-associated antigens (TAAs)...
February 15, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28215653/dendritic-cells-infected-by-ad-sh-socs1-enhance-cytokine-induced-killer-cik-cell-immunotherapeutic-efficacy-in-cervical-cancer-models
#11
Yi Zheng, Bicheng Hu, Shenggao Xie, Xiaofan Chen, Yuqian Hu, Wanping Chen, Shanshan Li, Bo Hu
BACKGROUND AIMS: Cervical cancer constitutes a major problem in women's health worldwide, but the efficacy of the standard therapy is unsatisfactory. Cytokine-induced killer (CIK) cells exhibit antitumor activity against a variety of malignancies in preclinical models and have proven safe and effective in clinical trials. However, current CIK therapy has limitations and needs to be improved to meet the clinical requirements. The aim of this study was to investigate whether suppressing the expression of cytokine signaling 1 (SOCS1) in dendritic cells (DCs) can shorten in vitro CIK culture time and improve its antitumor efficacy...
February 15, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28215530/rationale-for-the-combination-of-dendritic-cell-based-vaccination-approaches-with-chemotherapy-agents
#12
I Truxova, M Hensler, P Skapa, M J Halaska, J Laco, A Ryska, R Spisek, J Fucikova
Owing to their central role in the initiation and regulation of antitumor immunity, dendritic cells (DCs) have been widely tested for use in cancer immunotherapy. Despite several encouraging clinical applications, existing DC-based immunotherapy efforts have yielded inconsistent results. Recent work has identified strategies that may allow for more potent DC-based vaccines, such as the combination with antitumor agents that have the potential to synergistically enhance DC functions. Selected cytotoxic agents may stimulate DCs either by directly promoting their maturation or through the induction of immunogenic tumor cell death...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28214928/dendritic-cell-rehab-new-strategies-to-unleash-therapeutic-immunity-in-ovarian-cancer
#13
REVIEW
Chang-Suk Chae, Eli Teran-Cabanillas, Juan R Cubillos-Ruiz
Immune-based therapies that induce remarkable and durable responses against melanoma and lung cancer have unfortunately demonstrated limited success in ovarian cancer patients. This is likely due to the exceptional immunoregulatory nature of ovarian tumors, which employ numerous strategies to effectively suppress anti-tumor immunity. Here, we summarize a decade of research indicating that ovarian cancers possess an exquisite capacity to subvert the activity of host dendritic cells (DCs) as a key mechanism to impede the development and maintenance of protective T cell-based immune responses...
February 18, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28214774/multimodality-imaging-of-bone-marrow-derived-dendritic-cell-migration-and-antitumor-immunity
#14
Su-Bi Ahn, Sang Bong Lee, Thoudam Debraj Singh, Sung Jin Cho, Sang Kyoon Kim, In-Kyu Lee, Shin Young Jeong, Byeong-Cheol Ahn, Jaetae Lee, Sang-Woo Lee, Yong Hyun Jeon
Here, we sought to monitor bone marrow-derived dendritic cell (BMDC) migration and antitumor effects using a multimodal reporter imaging strategy in living mice. BMDCs were transduced with retroviral vector harboring human sodium iodide symporter (hNIS, nuclear imaging reporter), firefly luc2 (optical imaging reporter), and thy1.1 (surrogate marker of NIS and luc2) genes (BMDC/NF cells). No significant differences in biological functions, including cell proliferation, antigen uptake, phenotype expression, and migration ability, were observed between BMDC and BMDC/NF cells...
February 16, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28214198/tumor-derived-cd4-cd25-regulatory-t-cells-inhibit-dendritic-cells-function-by-ctla-4
#15
Xin Chen, Yong Du, Qingqing Hu, ZhiMing Huang
PURPOSE: CD4+CD25+regulatoryT cells (Tregs) play an important role in anti-tumor immune responses. Poor prognosis and declining survival rates have intimate connection with high Treg expression in cancer patients. Cytotoxic T Lymphocyte-associated protein (CTLA-4) is one of the most prominent molecules on Treg. In our previous research, we have demonstrated that HCC-derived Tregs can interfere with Dendritic cells (DCs) function and down-modulate CD80/CD86 on DCs in vitro in a cell-contact dependent way...
December 21, 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28213366/tumor-infiltrating-and-peripheral-blood-t-cell-immunophenotypes-predict-early-relapse-in-localized-clear-cell-renal-cell-carcinoma
#16
Nicolas A Giraldo, Etienne Becht, Yann Vano, Florent Petitprez, Laetitia Lacroix, Pierre Validire, Rafael Sanchez-Salas, Alexandre Ingels, Stephane Marie Oudard, Audrey Moatti, Bénédicte Buttard, Sarah Bourras, Claire Germain, Xavier Cathelineau, Wolf-Herman Fridman, Catherine Sautes-Fridman
PURPOSE: The efficacy of PD-1 Checkpoint Blockade (ChB) as adjuvant therapy in localized clear cell Renal Cell Carcinoma (ccRCC) is currently unknown. The identification of tumor microenvironment (TME) prognostic biomarkers in this setting may help to define which patients could benefit from ChB and to uncover new therapeutic targets. EXPERIMENTAL DESIGN: We performed multiparametric flow cytometry immunophenotypic analysis of T cells isolated from tumor tissue (TIL), adjacent non-malignant renal tissue (RIL) and peripheral blood (PBL), in a cohort of patients (n=40) with localized ccRCC...
February 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28205361/immunotherapy-against-metastatic-bladder-cancer-by-combined-administration-of-granulocyte-macrophage-colony-stimulating-factor-and-interleukin-2-surface-modified-mb49-bladder-cancer-stem-cells-vaccine
#17
Chun-Yan Wang, Rui Hua, Li Liu, Xiaomin Zhan, Simei Chen, Song Quan, Qing-Jun Chu, Yong-Tong Zhu
In previous studies, it has been shown that the granulocyte macrophage-colony stimulating factor (GM-CSF) or interleukin-2 (IL-2) surface modified MB49 bladder cancer stem cells (MCSCs) vaccine could induce a specific antitumor immunity and against bladder cancer in mice model respectively. However, whether combined administration of GM-CSF and IL-2 could produce specific immune responses to cancer stem cells (CSCs) was uncertain. MCSCs were established and characterized. GM-CSF and IL-2 MCSCs vaccines were prepared and bioactivity was evaluated...
February 16, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28203287/specific-immunotherapy-in-renal-cancer-a-systematic-review
#18
REVIEW
Armin Hirbod-Mobarakeh, Hesam Addin Gordan, Zahra Zahiri, Mohammad Mirshahvalad, Sima Hosseinverdi, Brian I Rini, Nima Rezaei
BACKGROUND: Renal cell cancer (RCC) is the tenth most common malignancy in adults. In recent years, several approaches of active and passive immunotherapy have been studied extensively in clinical trials of patients with RCC. The aim of this systematic review was to assess the clinical efficacy of various approaches of specific immunotherapy in patients with RCC. METHODS: We searched Medline, Scopus, CENTRAL, TRIP, DART, OpenGrey and ProQuest without any language filter through to 9 October 2015...
February 2017: Therapeutic Advances in Urology
https://www.readbyqxmd.com/read/28202532/cd40-signaling-drives-potent-cellular-immune-responses-in-heterologous-cancer-vaccinations
#19
Supot Nimanong, Dmitrij Ostroumov, Jessica Wingerath, Sarah Knocke, Norman Woller, Engin Guerlevik, Christine Falk, Michael P Manns, Florian Kuehnel, Thomas C Wirth
Antagonistic antibodies targeting co-inhibitory receptors have revolutionized the treatment of cancer by inducing durable immune responses and clinical remissions in patients. In contrast, success of agonistic costimulatory antibodies has thus far been limited due to insufficient induction of adaptive immune responses. Here we describe a novel vaccination method consisting of a primary dendritic cell immunization followed by a composite vaccination including an agonistic CD40 antibody, soluble antigen and a TLR3 agonist, referred to as CoAT...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28201977/targeting-the-immune-niche-within-the-bone-marrow-microenvironment-the-rise-of-immunotherapy-in-multiple-myeloma
#20
Klaus Podar, D Jäger
Multiple Myeloma (MM) cells inhibit the development of an effective anti-MM immune response via defects in T cell function, ineffective antigen presentation; reduced phagocytic capacity; natural killer and dendritic cell dysfunction; decreased responsiveness to IL-2 and defects in B cell immunity; upregulation of inhibitory pathways; and production of excessive pro-inflammatory cytokines. Moreover, immune cells including plasmacytoid dendritic cells and macrophages trigger tumor cell proliferation, survival, and drug resistance...
February 13, 2017: Current Cancer Drug Targets
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