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Anti-tumor vaccines

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https://www.readbyqxmd.com/read/29782143/anti-tumor-humoral-and-t-cell-responses-by-mucin-1-conjugates-of-bacteriophage-qb-in-wildtype-mice
#1
Zhaojun Yin, Xuanjun Wu, Katarzyna Kaczanowska, Suttipun Sungsuwan, Marta Comellas-Aragones, Christian Pett, Jin Yu, Claire Baniel, Ulrika Westerlind, M G Finn, Xuefei Huang
Mucin-1 (MUC1) is one of the top ranked tumor associated antigens. In order to generate effective anti-MUC1 immune responses as potential anti-cancer vaccines, MUC1 peptides and glycopeptides have been covalently conjugated to bacteriophage Qb. Immunization of mice with these constructs led to highly potent antibody responses with IgG titers over one million, which are among the highest anti-MUC1 IgG titers reported to date. Furthermore, the high IgG antibody levels persisted for more than six months. The constructs also elicited MUC1 specific cytotoxic T cells, which can selectively kill MUC1 positive tumor cells...
May 21, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29778570/nitrated-t-helper-cell-epitopes-enhance-the-immunogenicity-of-her2-vaccine-and-induce-anti-tumor-immunity
#2
Hong Tian, Yu He, Xiaoda Song, Liangliang Jiang, Jianhua Luo, Yi Xu, Wanli Zhang, Xiangdong Gao, Wenbing Yao
Human epidermal growth factor receptor 2 (HER2) is an attractive target for cancer vaccine. However, autoimmune tolerance prevents vaccines based on HER2 protein from inducing long-lasting, highly effective anti-tumor immunity. In this study, we proved that the introduction of p-nitrophenylalanine in the universal T cell epitope (named NitraTh) enhances humoral immunity induced by B cell epitope and cellular immunity induced by CTL epitope. Moreover, this NitraTh epitope can work in both mouse and human immune system...
May 17, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29773448/the-role-of-the-common-gamma-chain-family-cytokines-in-%C3%AE-%C3%AE-t-cell-based-anti-cancer-immunotherapy
#3
REVIEW
Heleen H Van Acker, Diana Campillo-Davo, Gils Roex, Maarten Versteven, Evelien L Smits, Viggo F Van Tendeloo
Cytokines of the common gamma-chain receptor family, comprising interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15 and IL-21, are vital with respect to organizing and sustaining healthy immune cell functions. Supporting the anti-cancer immune response, these cytokines inspire great interest for their use as vaccine adjuvants and cancer immunotherapies. It is against this background that gamma delta (γδ) T cells, as special-force soldiers and natural contributors of the tumor immunosurveillance, also received a lot of attention the last decade...
May 14, 2018: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/29772538/targeting-fibroblast-activation-protein-in-cancer-prospects-and-caveats
#4
Petr Busek, Rosana Mateu, Michal Zubal, Lenka Kotackova, Aleksi Sedo
Fibroblast activation protein (FAP, seprase) is a serine protease with post-proline dipeptidyl peptidase and endopeptidase enzymatic activity. FAP is upregulated in several tumor types, while its expression in healthy adult tissues is scarce. FAP molecule itself and FAP+ stromal cells play an important although probably context-dependent and tumor type-specific pathogenetic role in tumor progression. We provide an overview of FAP expression under both physiological and pathological conditions with focus on human malignancies...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29769207/mitigating-sox2-potentiated-immune-escape-of-head-and-neck-squamous-cell-carcinoma-with-a-sting-inducing-nanosatellite-vaccine
#5
Yee Sun Tan, Kanokwan Sansanaphongpricha, Yuying Xie, Christopher R Donnelly, Xiaobo Luo, Blake R Heath, Xinyi Zhao, Emily L Bellile, Hongxiang Hu, Hongwei Chen, Peter J Polverini, Qianming Chen, Simon Young, Thomas E Carey, Jacques E Nör, Robert L Ferris, Gregory Wolf, Duxin Sun, Yu L Lei
PURPOSE: The response rates of Head and Neck Squamous Cell Carcinoma (HNSCC) to checkpoint blockade are below 20%. We aim to develop a mechanism-based vaccine to prevent HNSCC immune escape. EXPERIMENTAL DESIGN: We performed RNA-Seq of sensitive and resistant HNSCC cells to discover central pathways promoting resistance to immune killing. Using biochemistry, animal models, HNSCC microarray and immune cell deconvolution, we assessed the role of SOX2 in inhibiting STING-type I interferon (IFN-I) signaling-mediated anti-tumor immunity...
May 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29768704/syntheses-and-immunological-evaluation-of-self-adjuvanting-clustered-n-acetyl-and-n-propionyl-sialyl-tn-combined-with-a-t-helper-cell-epitope-as-antitumor-vaccine-candidates
#6
Tsung-Che Chang, Yoshiyuki Manabe, Yukari Fujimoto, Shino Ohshima, Yoshie Kametani, Kazuya Kabayama, Yuka Nimura, Chun-Cheng Lin, Koichi Fukase
Sialyl-Tn (STn) is a tumor-associated carbohydrate antigen (TACA) rarely observed on healthy tissues. We synthesized two fully synthetic N-acetyl and N-propionyl STn trimer (triSTn) vaccines possessing a T-helper epitope and a TLR2 agonist, since the clustered STn antigens are highly expressed on many cancer cells. Immunization of both vaccines in mice induced the anti-triSTn IgG antibodies, which recognized triSTn-expressing cell lines PANC-1 and HepG2. The N-propionyl triSTn vaccine induced the triSTn-specific IgGs, while IgGs induced by the N-acetyl triSTn vaccine were less specific...
May 16, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29764863/extracorporeal-photochemotherapy-drives-monocyte-to-dendritic-cell-maturation-to-induce-anti-cancer-immunity
#7
Alessandra Ventura, Aaron Vassall, Eve Robinson, Renata Filler, Douglas Hanlon, Katrina Meeth, Harib Ezaldein, Michael Girardi, Olga Sobolev, Marcus W Bosenberg, Richard L Edelson
Extracorporeal photochemotherapy (ECP) is a cancer immunotherapy for cutaneous T cell lymphoma (CTCL) operative in more than 350 centers worldwide. While its efficacy and favorable safety profile have driven its widespread use, elucidation of its underlying mechanism has been difficult. In this study, we identify the principal contributors to the anti-cancer immunotherapeutic effects of ECP, with the goal of enhancing potency and broadening applicability to additional malignancies. First, we scaled down the clinical ECP leukocyte-processing device to mouse size...
May 15, 2018: Cancer Research
https://www.readbyqxmd.com/read/29764164/immunoregulatory-antigens-novel-targets-for-cancer-immunotherapy
#8
Ayako Wakatsuki Pedersen, Katharina L Kopp, Mads Hald Andersen, Mai-Britt Zocca
Historically, the development of cancer vaccines has focused on the central role of tumor antigens in eliciting tumor-specific immune responses, with limited success. Recent advances with checkpoint blockade approaches have brought about a renewed appreciation of the importance of targeting immune suppression in cancer patients. Here we discuss a novel approach to cancer immunotherapy, namely to target recently described T cells that uniquely control cells with immune suppressive functions. Accumulating evidence support the existence of self-reactive T cells that are specific to antigens derived from immunoregulatory proteins ("immunoregulatory antigens"), such as indoleamine 2,3-dioxygenase (IDO) and PD-L1...
April 2018: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/29763778/mage-a-antigens-as-targets-for-cancer-immunotherapy
#9
REVIEW
Erik Schooten, Alessia Di Maggio, Paul M P van Bergen En Henegouwen, Marta M Kijanka
Targeted anti-cancer therapies aim at reducing side effects while retaining their anti-cancer efficacy. Immunotherapies e.g. monoclonal antibodies, adoptive T cell therapy and cancer vaccines are used to combat cancer, but the number of available cancer specific targets is limited and new approaches are needed to generate more effective and patient tailored treatments. Unique cancer intracellular epitopes can be presented on the cell surface by MHC class I molecules, which can function as epitopes for targeted therapies...
April 26, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29760047/nanoparticles-that-reshape-the-tumor-milieu-create-a-therapeutic-window-for-effective-t-cell-therapy-in-solid-malignancies
#10
Fan Zhang, Sirkka B Stephan, Chibawanye I Ene, Tyrel T Smith, Eric C Holland, Matthias T Stephan
A major obstacle to the success rate of chimeric antigen receptor (CAR-) T cell therapy against solid tumors is the microenvironment antagonistic to T cells that solid tumors create. Conventional checkpoint blockade can silence lymphocyte anti-survival pathways activated by tumors, but because they are systemic, these treatments disrupt immune homeostasis and induce autoimmune side effects. Thus, new technologies are required to remodel the tumor milieu without causing systemic toxicities. Here we demonstrate that targeted nanocarriers that deliver a combination of immune-modulatory agents can remove pro-tumor cell populations and simultaneously stimulate anti-tumor effector cells...
May 14, 2018: Cancer Research
https://www.readbyqxmd.com/read/29758415/anti-tumor-effects-of-propranolol-adjuvant-activity-on-a-transplanted-murine-breast-cancer-model
#11
Somayeh Ashrafi, Reza Shapouri, Ahmad Shirkhani, Mehdi Mahdavi
Propranolol (Pro), a non-specific β-adrenergic blocking drug, competitively prevents the binding of catecholamines to receptors and suppresses cancer cells. The anti-tumor activity of propranolol has been proved in different kinds of cancers. In this study, we assessed the adjuvant activity of propranolol combined with a tumor vaccine model on the immunological parameters of breast tumor-bearing mice. Breast tumor pieces were implanted into the flank of inbred BALB/C female mice from stock mice. Tumor-bearing mice were treated with tumor antigen lysate vaccine and propranolol/Vaccine (Pro/Vac) combination (as treatment groups), propranolol and PBS (as control groups) for 5 consecutive days, every 12 h...
May 11, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29755693/exosomes-in-melanoma-a-role-in-tumor-progression-metastasis-and-impaired-immune-system-activity
#12
REVIEW
Marco Tucci, Francesco Mannavola, Anna Passarelli, Luigia Stefania Stucci, Mauro Cives, Franco Silvestris
Exosomes (Exo) are small vesicles produced by melanoma cells and the accessory cells of the tumor microenvironment. They emerge via both classical and direct pathways and actively participate in tumor colonisation of distant tissues. The proteins, nucleic acids, cytokines and growth factors engulfed by Exo are transferred to recipient cells, where they drive numerous functions required for the tumor escape from immune system control and tumor progression. By positively or negatively modulating immune cell properties, Exo provoke immune suppression and, in turn, defective dendritic cell (DC) functions...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29755666/impact-of-lenalidomide-maintenance-on-the-immune-environment-of-multiple-myeloma-patients-with-low-tumor-burden-after-autologous-stem-cell-transplantation
#13
Karel Fostier, Jo Caers, Nathalie Meuleman, Katrijn Broos, Jurgen Corthals, Kris Thielemans, Rik Schots, Brenda De Keersmaecker
Lenalidomide is a potent anti-myeloma drug with immunomodulatory properties. It is increasingly used in a low-dose maintenance setting to prolong remission duration after standard treatment. Data on the in vivo effects of lenalidomide are scarce and sometimes different from the well-described in vitro effects. We therefore evaluated the numerical, phenotypical and functional impact of lenalidomide maintenance on several immune cell types in a cohort of seventeen homogeneously treated myeloma patients achieving a low residual myeloma burden after a bortezomib based-induction followed by autologous stem cell transplantation...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29753042/application-of-e75-peptide-vaccine-in-breast-cancer-patients-a-systematic-review-and-meta-analysis
#14
REVIEW
Reyhane Chamani, Peyman Ranji, Maryam Hadji, Azin Nahvijou, Ebrahim Esmati, Ali Mohammad Alizadeh
The E75 peptide vaccine, derived from tumor-associated antigen HER2, is the most frequently studied anti-HER2 vaccination strategy for the treatment of breast cancer patients. It has been investigated in the several phases Ι/Π of the clinical trials and is currently being evaluated in a randomized multicenter phase III clinical trial. We conducted a systematic review and meta-analysis to clarify the outcomes of the E75 peptide vaccine including the therapeutic efficacy, the disease recurrence, the survival rate, and the side effects...
May 9, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29751136/anti-epidermal-growth-factor-vaccine-antibodies-enhance-the-efficacy-of-tyrosine-kinase-inhibitors-and-delay-the-emergence-of-resistance-in-egfr-mutant-lung-cancer-cells
#15
Jordi Codony-Servat, Silvia García-Roman, Miguel Ángel Molina-Vila, Jordi Bertran-Alamillo, Ana Giménez-Capitán, Santiago Viteri, Andrés F Cardona, Erik d'Hondt, Niki Karachaliou, Rafael Rosell
INTRODUCTION: Mutations in EGFR correlate with impaired response to immune checkpoint inhibitors and the development of novel immunotherapeutic approaches for EGFR mutant non-small cell lung cancer (NSCLC) is of particular interest. Immunization against EGF has demonstrated efficacy in a phase III trial including unselected NSCLC patients, but little was known about the mechanisms involved in the effects of the anti-EGF antibodies generated by vaccination (anti-EGF VacAbs) or their activity in tumor cells with EGFR mutations...
May 8, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29749436/production-of-an-anti-tm4sf5-monoclonal-antibody-and-its-application-in-the-detection-of-tm4sf5-as-a-possible-marker-of-a-poor-prognosis-in-colorectal-cancer
#16
Byoung Kwon Park, Jae-Young Park, Te Ha Kim, Dongbum Kim, Guang Wu, Avishekh Gautam, Sony Maharjan, Su In Lee, Younghee Lee, Hyung-Joo Kwon, Kyung Chan Choi
The cell surface transmembrane 4 superfamily member 5 protein (TM4SF5) has been implicated in various human cancers. Immunization with a peptide vaccine targeting human TM4SF5 has been shown to exert prophylactic and therapeutic effects against the development of hepatocellular carcinoma and colon cancer in mouse models. In this study, we developed a novel monoclonal antibody (mEC2‑CF) targeting a cyclic epitope of TM4SF5 and evaluated its reactivity to TM4SF5 in colorectal cancer (CRC) cells and cancer tissues...
April 26, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29748391/tumor-specific-inhibition-of-in-situ-vaccination-by-distant-untreated-tumor-sites
#17
Zachary S Morris, Emily I Guy, Lauryn R Werner, Peter M Carlson, Clinton M Heinze, Jasdeep S Kler, Sara M Busche, Abigail A Jaquish, Raghava N Sriramaneni, Lakeesha Carmichael, Hans Loibner, Stephen D Gillies, Alan J Korman, Amy K Erbe, Jacquelyn A Hank, Alexander L Rakhmilevich, Paul M Harari, Paul M Sondel
In situ vaccination is an emerging cancer treatment strategy that uses local therapies to stimulate a systemic antitumor immune response. We previously reported an in situ vaccination effect when combining radiation (RT) with intra-tumor (IT) injection of tumor-specific immunocytokine (IC), a fusion of tumor-specific antibody and IL2 cytokine. In mice bearing two tumors, we initially hypothesized that delivering RT plus IT-IC to the "primary" tumor would induce a systemic antitumor response causing regression of the "secondary" tumor...
May 10, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29731862/synergistic-anti-tumor-effects-of-dasatinib-and-dendritic-cell-vaccine-on-metastatic-breast-cancer-in-a-mouse-model
#18
Ningning Song, Hulin Guo, Jia Ren, Suhong Hao, Xinchao Wang
Immunotherapy is currently considered as one of the major anti-tumor modalities, but its efficacy is limited. Dasatinib could improve the expansion and recruitment of cluster of differentiation (CD) 8+ T cells and natural killer (NK) cells to the tumor microenvironment. The present study aimed to evaluate the synergistic anti-tumor effects of dasatinib with dendritic cell (DC) vaccine in metastatic breast cancer. Dasatinib with DC vaccine was administered to mice inoculated with 4T1 breast cancer cells. Thereafter, tumor volume was measured every other day...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29721396/m7824-a-novel-bifunctional-anti-pd-l1-tgf%C3%AE-trap-fusion-protein-promotes-anti-tumor-efficacy-as-monotherapy-and-in-combination-with-vaccine
#19
Karin M Knudson, Kristin C Hicks, Xiaoling Luo, Jin-Qiu Chen, Jeffrey Schlom, Sofia R Gameiro
Tumors evade host immune surveillance through multiple mechanisms, including the generation of a tumor microenvironment that suppresses immune effector function. Secretion of TGFβ and upregulation of immune checkpoint programmed cell death ligand-1 (PD-L1) are two main contributors to immune evasion and tumor progression. Here, we examined the efficacy of a first-in-class bifunctional checkpoint inhibitor, the fusion protein M7824, comprising the extracellular domain of human TGFβRII (TGFβ Trap) linked to the C-terminus of human anti-PD-L1 heavy chain (αPD-L1)...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29712687/cross-talk-between-t-cells-and-hematopoietic-stem-cells-during-adoptive-cellular-therapy-for-malignant-glioma
#20
Tyler J Wildes, Adam Grippin, Kyle A Dyson, Brandon M Wummer, David J Damiani, Rebecca S Abraham, Catherine Flores, Duane A Mitchell
PURPOSE: Adoptive T cell immunotherapy (ACT) has emerged as a viable therapeutic for peripheral and central nervous system (CNS) tumors. In peripheral cancers, optimal efficacy of ACT is reliant on dendritic cells (DCs) in the tumor microenvironment. However, the CNS is largely devoid of resident migratory DCs to function as antigen-presenting cells during immunotherapy. Herein, we demonstrate that cellular interactions between adoptively-transferred tumor-reactive T cells and bone marrow-derived HSPCs lead to the generation of potent intratumoral DCs within the CNS compartment...
April 30, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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