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Anti-tumor vaccines

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https://www.readbyqxmd.com/read/28201977/targeting-the-immune-niche-within-the-bone-marrow-microenvironment-the-rise-of-immunotherapy-in-multiple-myeloma
#1
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
https://www.readbyqxmd.com/read/28196735/gtl001-and-bivalent-cyaa-based-therapeutic-vaccine-strategies-against-human-papillomavirus-and-other-tumor-associated-antigens-induce-effector-and-memory-t-cell-responses-that-inhibit-tumor-growth
#2
Michaël Esquerré, Marie Momot, Anne Goubier, Christophe Gonindard, Stéphane Leung-Theung-Long, Yolande Misseri, Marie-Christine Bissery
GTL001 is a bivalent therapeutic vaccine containing human papillomavirus (HPV) 16 and HPV18 E7 proteins inserted in the Bordetella pertussis adenylate cyclase (CyaA) vector intended to prevent cervical cancer in HPV-infected women with normal cervical cytology or mild abnormalities. To be effective, therapeutic cervical cancer vaccines should induce both a T cell-mediated effector response against HPV-infected cells and a robust CD8(+) T-cell memory response to prevent potential later infection. We examined the ability of GTL001 and related bivalent CyaA-based vaccines to induce, in parallel, effector and memory CD8(+) T-cell responses to both vaccine antigens...
February 10, 2017: Vaccine
https://www.readbyqxmd.com/read/28188748/association-between-high-avidity-t-cell-receptors-induced-by-alpha-fetoprotein-derived-peptides-and-anti-tumor-effects-in-patients-with-hepatocellular-carcinoma
#3
Hidetoshi Nakagawa, Eishiro Mizukoshi, Eiji Kobayashi, Toshikatsu Tamai, Hiroshi Hamana, Tatsuhiko Ozawa, Hiroyuki Kishi, Masaaki Kitahara, Tatsuya Yamashita, Kuniaki Arai, Takeshi Terashima, Noriho Iida, Kazumi Fushimi, Atsushi Muraguchi, Shuichi Kaneko
BACKGROUND & AIMS: Levels of alpha fetoprotein (AFP) are measured for surveillance and diagnosis of hepatocellular carcinoma (HCC). We performed a phase 1 trial to evaluate the safety and efficacy of AFP-derived peptides as an anti-tumor vaccine for patients with advanced HCC, and characterized induction of AFP-specific T-cell receptors (TCRs). METHODS: We performed a prospective study, of 15 patients with HCC seen at Kanazawa University Hospital in Japan from March 2010 through March 2012...
February 7, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28187172/generation-of-dendritic-cell-based-vaccine-using-high-hydrostatic-pressure-for-non-small-cell-lung-cancer-immunotherapy
#4
Nada Hradilova, Lenka Sadilkova, Ondrej Palata, Dagmar Mysikova, Hana Mrazkova, Robert Lischke, Radek Spisek, Irena Adkins
High hydrostatic pressure (HHP) induces immunogenic death of tumor cells which confer protective anti-tumor immunity in vivo. Moreover, DC pulsed with HHP-treated tumor cells induced therapeutic effect in mouse cancer model. In this study, we tested the immunogenicity, stability and T cell stimulatory activity of human monocyte-derived dendritic cell (DC)-based HHP lung cancer vaccine generated in GMP compliant serum free medium using HHP 250 MPa. DC pulsed with HHP-killed lung cancer cells and poly(I:C) enhanced DC maturation, chemotactic migration and production of pro-inflammatory cytokines after 24h...
2017: PloS One
https://www.readbyqxmd.com/read/28185916/dna-vaccines-for-prostate-cancer
#5
REVIEW
Christopher D Zahm, Viswa Teja Colluru, Douglas G McNeel
DNA vaccines offer many advantages over other anti-tumor vaccine approaches due to their simplicity, ease of manufacturing, and safety. Results from several clinical trials in patients with cancer have demonstrated that DNA vaccines are safe and can elicit immune responses. However, to date few DNA vaccines have progressed beyond phase I clinical trial evaluation. Studies into the mechanism of action of DNA vaccines in terms of antigen-presenting cell types able to directly present or cross-present DNA-encoded antigens, and the activation of innate immune responses due to DNA itself, have suggested opportunities to increase the immunogenicity of these vaccines...
February 6, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28183282/enhanced-and-long-term-immunogenicity-of-a-her-2-neu-multi-epitope-vaccine-conjugated-to-the-carrier-crm197-in-conjunction-with-the-adjuvant-montanide
#6
Joshua Tobias, Joanna Jasinska, Karin Baier, Michael Kundi, Nicholas Ede, Christoph Zielinski, Ursula Wiedermann
BACKGROUND: We previously identified three short single peptides (P4, P6 and P7) representing different B-cell epitopes on the extracellular domain of Her-2/neu for a vaccine that was tested in a phase-I clinical trial. Here we describe the improvement of the multi peptide vaccine by fusing the single peptides to a hybrid peptide P467. METHODS: After coupling to either virosomes or to diphtheria toxoid CRM197 (CRM), the hybrid peptide was tested in different concentrations in combination with either Montanide or Aluminium hydroxide (Alum) in preclinical studies...
February 9, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28178658/prime-boost-immunization-by-both-dna-vaccine-and-oncolytic-adenovirus-expressing-gm-csf-and-shrna-of-tgf-%C3%AE-2-induces-anti-tumor-immune-activation
#7
So Young Kim, Dongxu Kang, Hye Jin Choi, Yeonsoo Joo, Joo-Hang Kim, Jae J Song
A successful DNA vaccine for the treatment of tumors should break established immune tolerance to tumor antigen. However, due to the relatively low immunogenicity of DNA vaccines, compared to other kinds of vaccines using live virus or protein, a recombinant viral vector was used to enhance humoral and cellular immunity. In the current study, we sought to develop a novel anti-cancer agent as a complex of DNA and oncolytic adenovirus for the treatment of malignant melanoma in the C57BL/6 mouse model. MART1, a human melanoma-specific tumor antigen, was used to induce an increased immune reaction, since a MART1-protective response is required to overcome immune tolerance to the melanoma antigen MelanA...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28178631/establishment-of-a-spontaneous-metastasis-tumor-model-for-human-erbb-2-vaccine
#8
Xin Dai, Yu He, Wenbing Yao, Xiangdong Gao
Human ErbB-2 (Her-2) is a critical target for cancer immunotherapy, and its over-expression can promote cancer migration and invasion. Compared with passive antibody therapy, vaccination treatment is more effective in the prevention of cancer recurrence. BALB-neuT mouse is a spontaneous metastasis tumor model used for testing the anti-tumor metastatic effect of rat ErbB-2 (neu) vaccine. However, no spontaneous metastasis tumor model used for evaluating Her-2 vaccine has been developed. In the current study, we attempted to use murine melanoma cell lines to establish a stable spontaneous metastasis tumor model for Her-2 vaccines...
February 5, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28176947/silencing-of-foxp3-enhances-the-antitumor-efficacy-of-gm-csf-genetically-modified-tumor-cell-vaccine-against-b16-melanoma
#9
Antonio Miguel, Luis Sendra, Verónica Noé, Carles J Ciudad, Francisco Dasí, David Hervas, María José Herrero, Salvador F Aliño
The antitumor response after therapeutic vaccination has a limited effect and seems to be related to the presence of T regulatory cells (Treg), which express the immunoregulatory molecules CTLA4 and Foxp3. The blockage of CTLA4 using antibodies has shown an effective antitumor response conducing to the approval of the human anti-CTLA4 antibody ipilimumab by the US Food and Drug Administration. On the other hand, Foxp3 is crucial for Treg development. For this reason, it is an attractive target for cancer treatment...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28159406/-the-anti-tumor-immune-response-in-breast-cancer-update-and-therapeutic-perspectives
#10
Sylvain Ladoire, Valentin Derangère, Laurent Arnould, Marion Thibaudin, Bruno Coudert, Veronique Lorgis, Isabelle Desmoulins, Marie Chaix, Pierre Fumoleau, François Ghiringhelli
The role of the immune response in breast cancer is now well recognized and increasingly taken in account. The goal of this article is, in the first part, to underline its prognostic impact and to precise the immunosurvelliance, immunoselection and the immunosubversion concepts involved in the control and evasion of breast carcinoma. In the second part, therapeutic strategies for the restauration of anti-tumor immunity are developed. Vaccination strategies and checkpoints inhibitors blockade strategies are discussed as well as the immunogenic death linked to the conventional treatments of breast cancer...
February 2017: Annales de Pathologie
https://www.readbyqxmd.com/read/28153581/delivery-of-tlr7-agonist-to-monocytes-and-dendritic-cells-by-dcir-targeted-liposomes-induces-robust-production-of-anti-cancer-cytokines
#11
Thomas C B Klauber, Janne M Laursen, Daniel Zucker, Susanne Brix, Simon S Jensen, Thomas L Andresen
: Tumor immune escape is today recognized as an important cancer hallmark and is therefore a major focus area in cancer therapy. Monocytes and dendritic cells (DCs), which are central to creating a robust anti-tumor immune response and establishing an anti-tumorigenic microenvironment, are directly targeted by the tumor escape mechanisms to develop immunosuppressive phenotypes. Providing activated monocytes and DCs to the tumor tissue is therefore an attractive way to break the tumor-derived immune suppression and reinstate cancer immune surveillance...
January 30, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28133807/host-controls-of-hiv-broadly-neutralizing-antibody-development
#12
REVIEW
Garnett Kelsoe, Barton F Haynes
Induction of broadly neutralizing antibodies (bNAbs) is a major goal of HIV vaccine development. BNAbs are made during HIV infection by a subset of individuals but currently cannot be induced in the setting of vaccination. Considerable progress has been made recently in understanding host immunologic controls of bNAb induction and maturation in the setting of HIV infection, and point to key roles for both central and peripheral immunologic tolerance mechanisms in limiting bnAb development. Immune tolerance checkpoint inhibition has been transformative in promotion of anti-tumor CD8 T-cell responses in the treatment of certain malignancies...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28129716/potential-and-clinical-translation-of-oncolytic-measles-viruses
#13
Steven Robinson, Evanthia Galanis
Oncolytic viruses represent a novel treatment modality that is unencumbered by the standard resistance mechanisms limiting the therapeutic efficacy of conventional antineoplastic agents. Attenuated engineered measles virus strains derived from the Edmonston vaccine lineage have undergone extensive preclinical evaluation and have demonstrated an ability to infect, resulting in antitumor effect with a broad variety of malignancies. They have laid the foundation for multiple future clinical trials in both solid and hematologic malignancies, which have demonstrated safety, biologic activity and the ability to elicit antitumor immune responses...
January 27, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28129129/intracellular-cleavable-cpg-oligodeoxynucleotide-antigen-conjugate-enhances-anti-tumor-immunity
#14
Katrin Kramer, Nicholas J Shields, Viola Poppe, Sarah L Young, Greg F Walker
Conjugation of a vaccine adjuvant to an antigen enhances anti-tumor immune responses. Direct chemical conjugation, however, may limit their processing by the antigen-presenting cell for immune stimulation. To test this hypothesis, antigen-adjuvant conjugates were designed to be cleaved by an intracellular trigger to release antigen and adjuvant from each other. The different reductive environment inside and outside antigen-presenting cells was used as a trigger for targeted intracellular release. Two redox-responsive disulphide linkers were used to conjugate the model antigen ovalbumin to CpG...
January 4, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28129128/aptamer-targeted-attenuation-of-il-2-signaling-in-cd8-t-cells-enhances-antitumor-immunity
#15
Anugraha Rajagopalan, Alexey Berezhnoy, Brett Schrand, Yvonne Puplampu-Dove, Eli Gilboa
Immune responses elicited against cancer using existing therapies such as vaccines or immune stimulatory antibodies are often not curative. One way to potentiate antitumor immunity is to enhance the long-term persistence of anti-tumor CD8(+) T cells. Studies have shown that the persistence of activated CD8(+) T cells is negatively impacted by the strength of interleukin 2 (IL-2) signaling. Here, we used small interfering RNAs (siRNAs) against CD25 (IL-2Rα) to attenuate IL-2 signaling in CD8(+) T cells. The siRNAs were targeted to 4-1BB-expressing CD8(+) T cells by conjugation to a 4-1BB-binding oligonucleotide aptamer...
January 4, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28126499/bacillus-calmette-guerin-improves-local-and-systemic-response-to-radiotherapy-in-invasive-bladder-cancer
#16
Barbara Prack Mc Cormick, Denise Belgorosky, Yanina Langle, Natalia Balarino, Eduardo Sandes, Ana María Eiján
BACKGROUND: A key factor contributing to radio-resistance in conservative invasive bladder cancer (BCa) treatment is tumor hypoxia and a strategy to overcome it is to trigger the production of nitric oxide (NO). On the other hand, ionizing radiation (IR) applied to a primary tumor can induce immunogenic cell death which may set off a cytotoxic immune response against the primary tumor and its metastasis. PURPOSE: To study in vitro and in vivo, the role of BCG as a local sensitizer to overcome hypoxia-associated radio-resistance through the production of NO, and as an immune-stimulator to be used in combination with IR to generate a local tumor vaccine for invasive BCa treatment...
January 23, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/28118089/the-revival-of-cancer-vaccines-the-eminent-need-to-activate-humoral-immunity
#17
Elisabeth J M Huijbers, Arjan W Griffioen
In light of the increasing number of approved monoclonal antibodies for the treatment of cancer, it seems peculiar that the development of antibody inducing vaccines get so little attention. In our view there is a tremendous opportunity in the development of cancer vaccines inducing humoral immune responses, involving a couple of major advantages. Firstly, the effectivity of a polyclonal antibody response is expected to exceed the one of monoclonal antibodies. This is supported by preclinical data that show pronounced anti-tumor responses and early clinical trials in which benefit is observed in patients with advanced cancer...
January 24, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28116088/radiotherapy-and-mva-muc1-il-2-vaccine-act-synergistically-for-inducing-specific-immunity-to-muc-1-tumor-antigen
#18
Gilda G Hillman, Lyndsey A Reich, Shoshana E Rothstein, Lisa M Abernathy, Matthew D Fountain, Kali Hankerd, Christopher K Yunker, Joseph T Rakowski, Eric Quemeneur, Philippe Slos
BACKGROUND: We previously demonstrated that tumor irradiation potentiates cancer vaccines using genetic modification of tumor cells in murine tumor models. To investigate whether tumor irradiation augments the immune response to MUC1 tumor antigen, we have tested the efficacy of tumor irradiation combined with an MVA-MUC1-IL2 cancer vaccine (Transgene TG4010) for murine renal adenocarcinoma (Renca) cells transfected with MUC1. METHODS: Established subcutaneous Renca-MUC1 tumors were treated with 8 Gy radiation on day 11 and peritumoral injections of MVA-MUC1-IL2 vector on day 12 and 17, or using a reverse sequence of vaccine followed by radiation...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28115578/immunosuppressive-tumor-infiltrating-myeloid-cells-mediate-adaptive-immune-resistance-via-a-pd-1-pd-l1-mechanism-in-glioblastoma
#19
Joseph P Antonios, Horacio Soto, Richard G Everson, Diana Moughon, Joey R Orpilla, Namjo P Shin, Shaina Sedighim, Janet Treger, Sylvia Odesa, Alexander Tucker, William H Yong, Gang Li, Timothy F Cloughesy, Linda M Liau, Robert M Prins
BACKGROUND: Adaptive immune resistance in the tumor microenvironment appears to attenuate the immunotherapeutic targeting of glioblastoma (GBM). In this study, we identified a tumor-infiltrating myeloid cell (TIM) population that expands in response to dendritic cell (DC) vaccine treatment. The aim of this study was to understand how this programmed death ligand 1 (PD-L1)-expressing population restricts activation and tumor-cytolytic function of vaccine-induced tumor-infiltrating lymphocytes (TILs)...
January 23, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28114249/inhibitors-of-cytotoxic-t-lymphocyte-antigen-4-and-programmed-death-1-programmed-death-1-ligand-for-metastatic-melanoma-dual-versus-monotherapy-summary-of-advances-and-future-directions-for-studying-these-drugs
#20
Kimberly Loo, Adil I Daud
Immense progress in the field of cancer immunotherapy has garnered several novel and successful treatments for metastatic melanoma. Beginning with therapies targeting cytotoxic T lymphocyte antigen 4 (CTLA-4), objective response rates, overall survival, and long-term survival were significantly increased when compared with glycoprotein 100 vaccine therapies. Expanding the breadth of therapies aimed to "release the breaks" on the active immune system, anti-programmed death 1 (PD-1) and anti-programmed death 1 ligand (PD-L1) therapies further improved overall survival, progression-free survival, and objective tumor response while exhibiting more favorable safety profiles compared with ipilimumab and to chemotherapy agents...
January 2017: Cancer Journal
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