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Anti-tumor vaccines

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https://www.readbyqxmd.com/read/28330372/car-t-cell-therapy-progress-and-prospects
#1
Olivia Wilkins, Allison May Keeler, Terence R Flotte
Lentivirus-mediated transduction of autologous T-cells with a chimeric antigen receptor (CAR) to confer a desired epitope-specificity as a targeted immunotherapy for cancer has been among the first human gene therapy techniques to demonstrate widespread therapeutic efficacy. Other approaches to using gene therapy to enhance anti-tumor immunity have been less specific and less effective. These included amplification, marking, and cytokine transduction of tumor infiltrating lymphocytes (TIL), recombinant virus-based expression of tumor antigens as a tumor vaccine, and transduction of antigen-presenting cells (APCs) with tumor antigens...
March 23, 2017: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/28321815/immune-therapy-for-sarcomas
#2
Peter M Anderson
Absolute lymphocyte count (ALC) recovery rapidly occurring at 14 days after start of chemotherapy for osteosarcoma and Ewing sarcoma is a good prognostic factor. Conversely, lymphopenia is associated with significantly decreased sarcoma survival. Clearly, the immune system can contribute towards better survival from sarcoma. This chapter will describe treatment and host factors that influence immune function and how effective local control and systemic interventions of sarcoma therapy can cause inflammation and/or immune suppression but are currently the standard of care...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28318492/-brain-tumor-immunotherapy-illusion-or-hope
#3
REVIEW
Denis Migliorini, Valérie Dutoit, Paul R Walker, Pierre-Yves Dietrich
Immunotherapy has proven efficient for many tumors and is now part of standard of care in many indications. What is the picture for brain tumors? The recent development of anti-CTLA-4 and PD1 immune checkpoint inhibitors, which have the ability to restore T lymphocytes activity, has gathered enthusiasm and is now paving the way towards more complex models of immune system manipulation. These models include, among others, vaccination and adoptive T cell transfer technologies. Complementary to those strategies, molecules capable of reshaping the immune tumor microenvironment are currently being investigated in early phase trials...
March 16, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28316990/diagnostic-and-therapeutic-biomarkers-in-glioblastoma-current-status-and-future-perspectives
#4
REVIEW
Wojciech Szopa, Thomas A Burley, Gabriela Kramer-Marek, Wojciech Kaspera
Glioblastoma (GBM) is a primary neuroepithelial tumor of the central nervous system, characterized by an extremely aggressive clinical phenotype. Patients with GBM have a poor prognosis and only 3-5% of them survive for more than 5 years. The current GBM treatment standards include maximal resection followed by radiotherapy with concomitant and adjuvant therapies. Despite these aggressive therapeutic regimens, the majority of patients suffer recurrence due to molecular heterogeneity of GBM. Consequently, a number of potential diagnostic, prognostic, and predictive biomarkers have been investigated...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28302019/the-breakthroughs-in-cancer-immune-checkpoint-based-therapy-a-review-of-development-in-immune-checkpoint-study-and-its-application
#5
Yao Huang, Dong Liang, Jingfeng Liu, Jinhua Zeng, Yongyi Zeng
Recently, immunotherapy has attracted more attentions to fight cancer due to its selectivity, long lasting effects, and demonstrated better overall survival and tolerance, when compared to patients treated with conventional chemotherapy or radiotherapy alone. The anti-tumor response of patient with cancer is improved either by increasing the effector cell number, the production of soluble mediators, or by modulating the host's immune checkpoint. Over the last decades, many new approaches in immunotherapy have been developed, such as immune checkpoint inhibitors, chimeric antigen receptor T cells (CART), specific T-cell -receptor T cells (TCRT) and cancer vaccine, some of which has been approved by FDA to treat several cancer types...
March 15, 2017: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/28299466/development-of-oral-cancer-vaccine-using-recombinant-bifidobacterium-displaying-wilms-tumor-1-protein
#6
Koichi Kitagawa, Tsugumi Oda, Hiroki Saito, Ayame Araki, Reina Gonoi, Katsumi Shigemura, Yoshiko Hashii, Takane Katayama, Masato Fujisawa, Toshiro Shirakawa
Several types of vaccine-delivering tumor-associated antigens (TAAs) have been developed in basic and clinical research. Wilms' tumor 1 (WT1), identified as a gene responsible for pediatric renal neoplasm, is one of the most promising TAA for cancer immunotherapy. Peptide and dendritic cell-based WT1 cancer vaccines showed some therapeutic efficacy in clinical and pre-clinical studies but as yet no oral WT1 vaccine can be administrated in a simple and easy way. In the present study, we constructed a novel oral cancer vaccine using a recombinant Bifidobacterium longum displaying WT1 protein...
March 15, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28298901/unveiling-another-missing-piece-in-ebv-driven-lymphomagenesis-ebv-encoded-micrornas-expression-in-eber-negative-burkitt-lymphoma-cases
#7
Lucia Mundo, Maria R Ambrosio, Matteo Picciolini, Giuseppe Lo Bello, Sara Gazaneo, Leonardo Del Porro, Stefano Lazzi, Mohsen Navari, Noel Onyango, Massimo Granai, Cristiana Bellan, Giulia De Falco, Davide Gibellini, Pier P Piccaluga, Lorenzo Leoncini
Epstein-Barr virus (EBV) is a gammaherpesvirus linked to a number of lymphoid and epithelial malignancies, including Burkitt lymphoma (BL) in which its frequency ranges from 30% in sporadic cases to 100% in the endemic ones. The possible contribution of EBV to BL pathogenesis is largely unknown. It has been suggested that EBV may be associated with all of the cases, including those diagnosed as EBV negative by a mechanism of hit-and-run. Early during oncogenesis, viral genes are essential for initiating disease...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28250921/transient-treg-depletion-enhances-therapeutic-anti-cancer-vaccination
#8
Scott A Fisher, Wayne J Aston, Jonathan Chee, Andrea Khong, Amanda L Cleaver, Jessica N Solin, Shaokang Ma, W Joost Lesterhuis, Ian Dick, Robert A Holt, Jenette Creaney, Louis Boon, Bruce Robinson, Richard A Lake
INTRODUCTION: Regulatory T cells (Treg) play an important role in suppressing anti- immunity and their depletion has been linked to improved outcomes. To better understand the role of Treg in limiting the efficacy of anti-cancer immunity, we used a Diphtheria toxin (DTX) transgenic mouse model to specifically target and deplete Treg. METHODS: Tumor bearing BALB/c FoxP3.dtr transgenic mice were subjected to different treatment protocols, with or without Treg depletion and tumor growth and survival monitored...
March 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28238782/vaccination-efficacy-with-marrow-mesenchymal-stem-cell-against-cancer-was-enhanced-under-simulated-microgravity
#9
Jing Li, Jun Chen, Xiuyu Li, Yanfang Qian
Stem cell vaccination can induce consistent and strong anti-tumor immunity against cancer in mice model. The antigenic similarity between tumors and embryos has been appreciated for many years and reflects the expression of embryonic gene products by cancer cells and/or cancer-initiating stem cells. Taking advantage of this similarity, we have tested a prophylactic lung cancer vaccine composed of allogeneic murine MSCs. Based on this conception, we first compared their tumor vaccines intervention effects of adult MSCs and MSCs under simulated microgravity (MSC/SMG)...
April 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28237837/a-novel-dna-vaccine-platform-enhances-neo-antigen-like-t-cell-responses-against-wt1-to-break-tolerance-and-induce-anti-tumor-immunity
#10
Jewell N Walters, Bernadette Ferraro, Elizabeth K Duperret, Kimberly A Kraynyak, Jaemi Chu, Ashley Saint-Fleur, Jian Yan, Hy Levitsky, Amir S Khan, Niranjan Y Sardesai, David B Weiner
Tumor-associated antigens have emerged as important immunotherapeutic targets in the fight against cancer. Germline tumor antigens, such as WT1, Wilms' tumor gene 1, are overexpressed in many human malignancies but have low expression in somatic tissues. Recent vaccination approaches to target WT1 have been hampered by poor in vivo immune potency, likely due to the conserved self-antigen nature of WT1. In this study, we use a novel synthetic micro-consensus SynCon DNA vaccine approach with the goal of breaking tolerance and increasing vaccine immune potency...
February 22, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28236573/modifying-antigen-encapsulating-liposomes-with-kala-facilitates-mhc-class-i-antigen-presentation-and-enhances-anti-tumor-effects
#11
Naoya Miura, Hidetaka Akita, Naho Tateshita, Takashi Nakamura, Hideyoshi Harashima
For a successful anti-cancer vaccine, antigen presentation on the major histocompatibility complex (MHC) class I is a requirement. To accomplish this, an antigen must be delivered to the cytoplasm by overcoming the endosome/lysosome. We previously reported that a lipid nanoparticle modified with a KALA peptide (WEAKLAKALAKALAKHLAKALAKALKA), an α-helical cationic peptide, permits the encapsulated pDNA to be efficiently delivered to the cytoplasm in bone marrow-derived dendritic cells (BMDCs). Herein, we report on the use of KALA-modified liposomes as an antigen carrier, in an attempt to induce potent antigen-specific cellular immunity...
February 21, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28231510/lipopolyplex-potentiates-anti-tumor-immunity-of-mrna-based-vaccination
#12
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...
May 2017: Biomaterials
https://www.readbyqxmd.com/read/28201977/targeting-the-immune-niche-within-the-bone-marrow-microenvironment-the-rise-of-immunotherapy-in-multiple-myeloma
#13
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
#14
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
#15
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
#16
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
#17
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 7, 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
#18
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
#19
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
#20
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...
April 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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