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https://www.readbyqxmd.com/read/28544973/pegylation-of-a-tlr2-agonist-based-vaccine-delivery-system-improves-antigen-trafficking-and-the-magnitude-of-ensuing-antibody-and-cd8-t-cell-responses
#1
Toshiki Sekiya, Junya Yamagishi, John Henry V Gray, Paul G Whitney, Axel Martinelli, Weiguang Zeng, Chinn Yi Wong, Chihiro Sugimoto, David C Jackson, Brendon Y Chua
The lipopeptide R4Pam2Cys is an agonist for toll-like receptor-2 (TLR2), a key pathogen-associated molecular pattern receptor expressed on many antigen-presenting cells such as dendritic cells (DCs). Electrostatic association of R4Pam2Cys with soluble protein antigens significantly enhances their immunogenicity and there is evidence to suggest that reducing the size of suitably adjuvanted-antigen complexes in solution may further improve their immunostimulatory capabilities. In this study, we investigated how incorporation of polyethylene glycol (PEG) into R4Pam2Cys affects the size, activity and efficacy of formed antigen-lipopeptide complexes...
May 11, 2017: Biomaterials
https://www.readbyqxmd.com/read/28536308/immune-correlates-of-gm-csf-and-melanoma-peptide-vaccination-in-a-randomized-trial-for-the-adjuvant-therapy-of-resected-high-risk-melanoma-e4697
#2
Lisa H Butterfield, Fengmin Zhao, Sandra Lee, Ahmad A Tarhini, Kim A Margolin, Richard L White, Michael Atkins, Gary I Cohen, Theresa L Whiteside, John M Kirkwood, David H Lawson
Purpose: E4697 was a multi-center intergroup randomized placebo-controlled Phase III trial of adjuvant GM-CSF and/or a multi-epitope melanoma peptide vaccine for patients with completely resected, high-risk stage III/IV melanoma. <p>Experimental Design: 815 patients were enrolled from 12/99 to 10/06 into this 6-arm study. GM-CSF was chosen to promote the numbers and functions of dendritic cells (DC). The melanoma antigen peptide vaccine (Tyrosinase368-376 (370D), gp100209-217 (210M), MART-127-35) in Montanide was designed to promote melanoma specific CD8(+) T cell responses...
May 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28536100/depletion-of-tumor-associated-macrophages-with-a-csf-1r-kinase-inhibitor-enhances-antitumor-immunity-and-survival-induced-by-dc-immunotherapy
#3
Floris Dammeijer, Lysanne A Lievense, Margaretha E H Kaijen-Lambers, Menno van Nimwegen, Koen Bezemer, Joost P Hegmans, Thorbald van Hall, Rudi W Hendriks, Joachim G Aerts
New immunotherapeutic strategies are needed to induce effective anti-tumor immunity in all cancer patients. Malignant mesothelioma is characterized by a poor prognosis and resistance to conventional therapies. Infiltration of tumor-associated macrophages (TAM) is prominent in mesothelioma and is linked to immune suppression, angiogenesis and tumor aggressiveness. Therefore, TAM depletion could potentially reactivate anti-tumor immunity. We show that M-CSFR-inhibition using the CSF-1R kinase inhibitor PLX3397 (pexidartinib) effectively reduced numbers of TAMs, circulating nonclassical monocytes, as well as amount of neo-angiogenesis and ascites in mesothelioma mouse models, but did not improve survival...
May 23, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28522585/herpes-simplex-virus-glycoprotein-d-targets-a-specific-dendritic-cell-subset-and-improves-the-performance-of-vaccines-to-human-papillomavirus-associated-tumors
#4
Bruna F M M Porchia, Ana Carolina R Moreno, Rodrigo N Ramos, Mariana O Diniz, Laís Helena T M de Andrade, Daniela S Rosa, José Alexandre M Barbuto, Silvia B Boscardin, Luís Carlos S Ferreira
Cervical cancer is a major public health problem and one of the leading causes of cancer deaths in women. Virtually all cases of cervical cancer, as well as a growing share of anal and head/neck tumors, are associated with human papillomavirus (HPV) infection. Despite the effectiveness, the available prophylactic vaccines do not benefit women with cervical lesions or cancer. Therefore, the search of new immunotherapeutic approaches to treat HPV-induced tumors is still a priority. The present study characterizes a therapeutic antitumor vaccine based on the genetic fusion of the Herpes simplex virus-1 (HSV-1) glycoprotein D (gD) with the E7 oncoprotein from HPV-16 (gDE7)...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28512265/chaetocin-enhances-dendritic-cell-function-via-the-induction-of-heat-shock-protein-and-cancer-testis-antigens-in-myeloma-cells
#5
Manh-Cuong Vo, Thanh-Nhan Nguyen-Pham, Hyun-Ju Lee, Sung-Hoon Jung, Nu-Ri Choi, My-Dung Hoang, Hyeoung-Joon Kim, Je-Jung Lee
Dendritic cells (DC)-based vaccines are considered useful in cancer immuno-therapy, and the interactions of DC and dying tumor cells are important and promising for cancer immunotherapy. We investigated whether chaetocin could be used to induce death of myeloma cells, for loading onto DCs can affect DCs function. In this study, we show that the dying myeloma cells treated with chaetocin resulted in the induction of heat shock protein (HSP) 90, which was inhibited by antioxidant N-acetyl cysteine, and showed an increase in the expression of MAGE-A3 and MAGE-C1/CT7...
April 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28511928/rational-design-of-nanoparticles-towards-targeting-antigen-presenting-cells-and-improved-t-cell-priming
#6
Eva Zupančič, Caterina Curato, Maria Paisana, Catarina Rodrigues, Ziv Porat, Ana S Viana, Carlos A M Afonso, João Pinto, Rogério Gaspar, João N Moreira, Ronit Satchi-Fainaro, Steffen Jung, Helena F Florindo
Vaccination is a promising strategy to trigger and boost immune responses against cancer or infectious disease. We have designed, synthesized and characterized aliphatic-polyester (poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP) to investigate how the nature of protein association (adsorbed versus entrapped) and polymer/surfactant concentrations impact on the generation and modulation of antigen-specific immune responses. The ability of the NP formulations to target dendritic cells (DC), be internalized and activate the T cells was characterized and optimized in vitro and in vivo using markers of DC activation and co-stimulatory molecules...
May 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28511091/molecular-cloning-and-characterization-of-dngr-1-in-rhesus-macaques
#7
Wen-Rong Yao, Lei Yu, Dong Li, Gui-Bo Yang
DC, NK lectin group receptor-1 (DNGR-1), also known as C-type lectin domain family 9 member A (CLEC9A), is a promising target for immunological therapeutics and vaccination against tumors and viruses. However, little is known about its property in rhesus macaques. In this study, we cloned rhesus macaque DNGR-1 cDNA, and found that its coding region could encode a 241-amino acid polypeptide with 91.7% sequence identity and similar antigenicity to that of humans. Both free and cell surface rhesus macaque DNGR-1 expressed in vitro could bind to apoptotic/dead cells induced by serum deprivation or freeze-thaw, and to pyroptotic cells stimulated with PMA and LPS...
May 13, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28504575/alleviation-of-enterotoxigenic-escherichia-coli-challenge-by-recombinant-lactobacillus-plantarum-expressing-a-faeg-and-dc-targeting-peptide-fusion-protein
#8
G Yang, Y Jiang, P Tong, C Li, W Yang, J Hu, L Ye, W Gu, C Shi, B Shan, C Wang
FaeG is the major subunit of K88 fimbriae. These cell surface attachments are considered to be the major virulence factor of enterotoxigenic Escherichia coli (ETEC), which causes diarrhoea in piglets. The use of dendritic cell-targeting peptide (DCpep) has been demonstrated to be an effective approach to enhance the immunity of vaccines. Lactobacillus plantarum is an attractive candidate for oral vaccination owing to its beneficial effects and safety. In this study, L. plantarum was employed to deliver a FaeG-DCpep fusion antigen, and the immune response in mice was evaluated...
May 15, 2017: Beneficial Microbes
https://www.readbyqxmd.com/read/28498414/nifuroxazide-prompts-antitumor-immune-response-of-tcl-loaded-dc-in-mice-with-orthotopically-implanted-hepatocarcinoma
#9
Tiesuo Zhao, Huijie Jia, Qian Cheng, Yali Xiao, Minming Li, Wenjing Ren, Chen Li, Yuchen Feng, Zhiwei Feng, Hui Wang, Junnian Zheng
Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with a poor prognosis and high mortality. At present, vaccination with tumor cell lysate (TCL) loaded dendritic cells (DC) has been shown to be an effective therapy against HCC. However, the ability of promoting the specific T cell immune response is rather weak, influencing the antitumor response. Thus, it is necessary to find a strategy to improve the antitumor effect of TCL-loaded DC. Activation of signal transducer and activator of transcription 3 (STAT3) significantly inhibits antitumor immune response and DC maturity...
May 5, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28495513/high-hydrostatic-pressure-affects-antigenic-pool-in-tumor-cells-implication-for-dendritic-cell-based-cancer-immunotherapy
#10
Linda Urbanova, Nada Hradilova, Irena Moserova, Sarka Vosahlikova, Lenka Sadilkova, Michal Hensler, Radek Spisek, Irena Adkins
High hydrostatic pressure (HHP) can be used to generate dendritic cell (DC)-based active immunotherapy for prostate, lung and ovarian cancer. We showed here that HHP treatment of selected human cancer cell lines leads to a degradation of tumor antigens which depends on the magnitude of HHP applied and on the cancer cell line origin. Whereas prostate or ovarian cell lines displayed little protein antigen degradation with HHP treatment up to 300MPa after 2h, tumor antigens are hardly detected in lung cancer cell line after treatment with HHP 250MPa at the same time...
May 8, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28480306/dendritic-cell-therapies-for-hematologic-malignancies
#11
REVIEW
Matthew Weinstock, Jacalyn Rosenblatt, David Avigan
Dendritic cells (DCs) are potent antigen-presenting cells that constitute a major component of the immune system's role in the recognition, elimination, and tolerance of cancer. The unique immunologic capabilities of DCs have recently been harnessed for therapeutic use with the creation of DC-based anti-tumor vaccines, several of which have moved into testing in clinical trials for hematologic malignancies. This review summarizes how treatment strategies using DC-based anti-tumor vaccines are advancing immunotherapeutic options for these diseases...
June 16, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28474788/in-vivo-targeting-of-protein-antigens-to-dendritic-cells-using-anti-dec-205-single-chain-antibody-improves-hiv-gag-specific-cd4-t-cell-responses-protecting-from-airway-challenge-with-recombinant-vaccinia-gag-virus
#12
Loveline N Ngu, Nadesh N Nji, Georgia E Ambada, Bertrand Sagnia, Carol Ngane Sake, Jules Colinc Tchadji, Ghislain Donald Njambe Priso, Abel Lissom, Thibau Flaurant Tchouangueu, Denis Manga Tebit, Alain Bopda Waffo, Chae Gyu Park, Ralph M Steinman, Klaus Überla, Godwin W Nchinda
INTRODUCTION: Targeting antigens to dendritic cells (DCs) in vivo via a DC-restricted endocytic receptor, DEC205, has been validated to enhance immunity in several vaccine platforms. Particularly atttractive is selected delivery of proteins to DCs in vivo because it enables proteins to be more immunogenic and provides a cheaper and effective way for repeated immunizations. METHODS: In this study, we tested the efficacy of a single chain antibody to DEC205 (scDEC) to deliver protein antigens selectively to DCs in vivo and to induce protective immunity...
March 13, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28468947/phase-i-trial-of-intratumoral-injection-of-ccl21-gene-modified-dendritic-cells-in-lung-cancer-elicits-tumor-specific-immune-responses-and-cd8-t-cell-infiltration
#13
Jay Moon M Lee, Mi-Heon Lee, Edward Garon, Jonathan W Goldman, Ramin Salehi-Rad, Felicita E Baratelli, Dorthe Schaue, Gerald Wang, Fran Rosen, Jane Yanagawa, Tonya C Walser, Ying Lin, Stacy J Park, Sharon Adams, Francesco M Marincola, Paul C Tumeh, Fereidoun Abtin, Robert Suh, Karen L Reckamp, Gina Lee, William D Wallace, Sarah Lee, Gang Zeng, David A Elashoff, Sherven Sharma, Steven M Dubinett
PURPOSE: A phase I study was conducted to determine safety, clinical efficacy, and anti-tumor immune responses in patients with advanced non-small cell lung carcinoma (NSCLC) following intratumoral (IT) administration of autologous dendritic cells (DC) transduced with an adenoviral (Ad) vector expressing the CCL21 gene (Ad-CCL21-DC). We evaluated safety and tumor antigen-specific immune responses following in situ vaccination (ClinicalTrials.gov: NCT01574222). EXPERIMENTAL DESIGN: Sixteen stage IIIB/IV NSCLC subjects received two vaccinations (1 x 106, 5 x 106, 1 x 107, or 3 x 107 dendritic cells/injection) by CT- or bronchoscopic-guided IT injections (days 0 and 7)...
May 3, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28460478/combination-therapy-with-dendritic-cells-and-lenalidomide-is-an-effective-approach-to-enhance-antitumor-immunity-in-a-mouse-colon-cancer-model
#14
Manh-Cuong Vo, Thanh-Nhan Nguyen-Pham, Hyun-Ju Lee, Thangaraj Jaya Lakshmi, Seoyun Yang, Sung-Hoon Jung, Hyeoung-Joon Kim, Je-Jung Lee
In this study, we investigated efficacy of lenalidomide in combination with tumor antigen-loaded dendritic cells (DCs) in murine colon cancer model. MC-38 cell lines were injected subcutaneously to establish colon cancer-bearing mice. After tumor growth, lenalidomide (50 mg/kg/day) was injected intraperitoneally on 3 consecutive days in combination with tumor antigen-loaded DC vaccination on days 8, 12, 16, and 20. The tumor antigen-loaded DCs plus lenalidomide combination treatment exhibited a significant inhibition of tumor growth compared with the other groups...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28458053/overexpression-of-ebola-virus-envelope-gp1-protein
#15
Zhongcheng Zou, John Misasi, Nancy Sullivan, Peter D Sun
Ebola virus uses its envelope GP1 and GP2 for viral attachment and entry into host cells. Due to technical difficulty expressing full-length envelope, many structural and functional studies of Ebola envelope protein have been carried out primarily using GP1 lacking its mucin-like domain. As a result, the viral invasion mechanisms involving the mucin-like domain are not fully understood. To elucidate the role of the mucin-like domain of GP1 in Ebola-host attachment and infection and to facilitate vaccine development, we constructed a GP1 expression vector containing the entire attachment region (1-496)...
April 27, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28457909/critical-role-for-skin-derived-migratory-dcs-and-langerhans-cells-in-tfh-and-gc-responses-after-intradermal-immunization
#16
Clément Levin, Olivia Bonduelle, Charles Nuttens, Charlotte Primard, Bernard Verrier, Alexandre Boissonnas, Béhazine Combadière
Intradermal (ID) delivery of antigen represents a potent route of immunization that involves multiple blood- and skin-derived dendritic cell (DC) sub-populations endowed with specialized functions and dynamics in their ability to prime naïve CD4+ T cells in the draining lymph node (DLN). Yet, their individual contributions to the generation of CD4+ T follicular helper (TFH) cells and germinal centers (GCs) remain to be understood. We found that ID immunization of mice with a particle-based vaccine induced robust TFH and GC B cell responses in skin DLNs, which were completely abrogated when skin cell emigration was prevented...
April 27, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28457810/chronic-stress-suppresses-anti-tumor-tcd8-responses-and-tumor-regression-following-cancer-immunotherapy-in-a-mouse-model-of-melanoma
#17
Annette Sommershof, Lisa Scheuermann, Julia Koerner, Marcus Groettrup
Animal tumor models and human cancer studies have provided convergent evidence that chronic psychological stress plays a decisive role in modulating anti-tumor T cell immunity. However, whether chronic stress also affects anti-cancer vaccine strategies that rely on the induction of functional tumor-specific TCD8+ cells has not been investigated yet. In this study we provide direct evidence that chronic stress suppresses the therapeutic efficacy of a biodegradable poly(d,l-lactide-co-glycolide) microsphere (PLGA-MS) based cancer vaccine in a murine melanoma model...
April 27, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28456076/a-novel-antigen-delivery-system-induces-strong-humoral-and-ctl-immune-responses
#18
Zishan Yang, Miaomiao Xu, Zhenghu Jia, Yuting Zhang, Li Wang, Hongru Zhang, Jingya Wang, Mei Song, Yapu Zhao, Zhenzhou Wu, Liqing Zhao, Zhinan Yin, Zhangyong Hong
New strategies with the ability to enhance both the humoral and cellular immune responses remain a priority for the development of future therapeutic cancer vaccines. In this study, we took advantage of β-glucan particles (GPs) derived from Saccharomyces cerevisiae baker's yeast and a novel reverse micro-emulsion method to prepare an antigen-loaded GP carrier system for dendritic cell (DC) specific antigen delivery, followed by careful evaluation of the immune functions of the prepared particles in initiating both the humoral and cellular immune responses through in vitro and in vivo experiments...
April 22, 2017: Biomaterials
https://www.readbyqxmd.com/read/28454381/optimized-construction-of-muc1-vntrn-dna-vaccine-and-its-anti-pancreatic-cancer-efficacy
#19
Yuan-Feng Gong, Quan-Bo Zhou, Ya-Di Liao, Cong Mai, Tie-Jun Chen, Yun-Qiang Tang, Ru-Fu Chen
Considering mucin 1-variable number tandem repeat (MUC1-VNTRn) as a novel target for pancreatic cancer immunotherapy, the present study aimed to screen and identify the pVAX1-MUC1-VNTRn DNA vaccine with the strongest immunogenicity. Following construction of a pVAX1-MUC1-VNTRn plasmid, immature dendritic cells (DCs) were subjected to transfection, and mature DCs were then co-cultured with autologous T-cells. The numbers of cytotoxic T lymphocytes (CTLs) secreting interferon (IFN)-γ were determined using an enzyme-linked immunospot assay, and CytoTox(®) was also used to examine the MUC1-VNTRn-specific Lethal effect of CTLs on Capan2 cells...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28445973/plasmodium-parasite-as-an-effective-hepatocellular-carcinoma-antigen-glypican-3-delivery-vector
#20
Quan Liu, Yijun Yang, Xuefang Tan, Zhu Tao, Dickson Adah, Songlin Yu, Junnan Lu, Siting Zhao, Limei Qin, Li Qin, Xiaoping Chen
We have previously demonstrated that malaria parasite infection has an anti-tumor effect in a mouse model. This research aimed to investigate the possibility of using Plasmodium parasite as a novel vaccine vector for hepatocellular carcinoma (HCC) immunotherapy. We constructed a Plasmodium yoelii 17XNL strain (P.y) expressing murine glypican-3 (GPC3) protein (P.y-GPC3), and examined its therapeutic potency in a murine Hepa1-6-induced hepatoma model that highly expressed GPC3 protein. The prerequisites for invoking a CD8+ T cell response were assessed after P...
April 11, 2017: Oncotarget
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