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Anti-tumor vaccines

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https://www.readbyqxmd.com/read/28734176/cancer-immunotherapy-moving-forward-with-peptide-t-cell-vaccines
#1
REVIEW
Takumi Kumai, Aaron Fan, Yasuaki Harabuchi, Esteban Celis
Recent advances in cancer immunology, such as the discovery of immune checkpoint inhibitors, have validated immune cells as potential key players for effective cancer treatment. The efficacy of these therapies seems to be codependent on a tumor-reactive T lymphocyte response. For many years, numerous attempts and strategies in developing vaccines to generate tumor-reactive T cells have yielded poor results in the clinic due to suboptimal immunogenicity and the inability to overcome an immunosuppressive tumor microenvironment...
July 19, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28732279/turbocharging-vaccines-emerging-adjuvants-for-dendritic-cell-based-therapeutic-cancer-vaccines
#2
REVIEW
Mansi Saxena, Nina Bhardwaj
Development of therapeutic cancer vaccines has been hindered by the many pro-tumorigenic mechanisms at play in cancer patients that serve to suppress both antigen presenting cells and T cells. In face of these obstacles, cancer vaccines are most likely to promote anti-tumorigenic immune responses only when formulated with strong adjuvants, and in combination with new immune interventions designed to reverse immune suppression and exhaustion of T cells in the tumor microenvironment. Dendritic cells (DCs) are often termed 'nature's adjuvant' due to their exceptional capacity for initiating both innate and adaptive immune responses...
July 18, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28732046/qualitative-differences-in-cellular-immunogenicity-elicited-by-hepatitis-c-virus-t-cell-vaccines-employing-prime-boost-regimens
#3
Wendy G Tan, Iryna Zubkova, Alla Kachko, Frances Wells, Heiko Adler, Gerd Sutter, Marian E Major
T-cell based vaccines have been considered as attractive candidates for prevention of hepatitis C virus (HCV) infections. In this study we compared the magnitude and phenotypic characteristics of CD8+ T-cells induced by three commonly used viral vectors, Adenovirus-5 (Ad5), Vaccinia virus (VV) and Modified Vaccinia Ankara (MVA) expressing the HCV NS3/4A protein. C57/BL6 mice were primed with DNA expressing NS3/4A and boosted with each of the viral vectors in individual groups of mice. We then tracked the vaccine-induced CD8+ T-cell responses using pentamer binding and cytokine production analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28725429/pretreatment-antigen-specific-immunity-and-regulation-association-with-subsequent-immune-response-to-anti-tumor-dna-vaccination
#4
Laura E Johnson, Brian M Olson, Douglas G McNeel
BACKGROUND: Immunotherapies have demonstrated clinical benefit for many types of cancers, however many patients do not respond, and treatment-related adverse effects can be severe. Hence many efforts are underway to identify treatment predictive biomarkers. We have reported the results of two phase I trials using a DNA vaccine encoding prostatic acid phosphatase (PAP) in patients with biochemically recurrent prostate cancer. In both trials, persistent PAP-specific Th1 immunity developed in some patients, and this was associated with favorable changes in serum PSA kinetics...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28720686/oncolytic-virus-induced-cell-death-and-immunity-a-match-made-in-heaven
#5
REVIEW
Jolien De Munck, Alex Binks, Iain A McNeish, Joeri L Aerts
Our understanding of the mechanisms responsible for cancer development has increased enormously over the last decades. However, for many cancers, this has not been translated into a significant improvement in overall survival, and overall mortality remains high. Treatment for many malignancies remains based on surgery, chemotherapy, and radiotherapy. Significant progress has been made toward the development of more specific, more potent, and less invasive treatment modalities, but such targeted therapies remain the exception for most cancers...
July 18, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28718331/entinostat-for-the-treatment-of-breast-cancer
#6
Dario Trapani, Angela Esposito, Carmen Criscitiello, Luca Mazzarella, Marzia Locatelli, Ida Minchella, Saverio Minucci, Giuseppe Curigliano
Breast cancer accounts for 29% of malignant tumors. It is an heterogenous disease covering a spectrum of different molecular subtypes. Epigenetic aberrations may affect gene expression through DNA and histone proteins modifications thus promoting tumor progression and resistance to anti- tumor treatment. Area covered: This article explores the potential role of entinostat in the treatment of breast cancer. The clinical trials evaluating entinostat are discussed, highlighting preclinical data and early-phase clinical studies results...
July 24, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28716080/pretreatment-antigen-specific-immunity-and-regulation-association-with-subsequent-immune-response-to-anti-tumor-dna-vaccination
#7
Laura E Johnson, Brian M Olson, Douglas G McNeel
BACKGROUND: Immunotherapies have demonstrated clinical benefit for many types of cancers, however many patients do not respond, and treatment-related adverse effects can be severe. Hence many efforts are underway to identify treatment predictive biomarkers. We have reported the results of two phase I trials using a DNA vaccine encoding prostatic acid phosphatase (PAP) in patients with biochemically recurrent prostate cancer. In both trials, persistent PAP-specific Th1 immunity developed in some patients, and this was associated with favorable changes in serum PSA kinetics...
July 18, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28714919/overcoming-oncogenic-mediated-tumor-immunity-in-prostate-cancer
#8
REVIEW
Geoffrey Bryant, Lin Wang, David J Mulholland
Immunotherapy is being tested intensively in clinical trials for prostate cancer; it includes immune checkpoint inhibition, prostate specific antigen (PSA) vaccines and dendritic cell-based strategies. Despite increasing evidence for clinical responses, the consensus of multiple trials is that prostate cancers are poorly responsive to immunotherapy. Prostate cancer has a high degree of pathological and genetic heterogeneity compared to other cancer types, which may account for immunotherapeutic resistance. This hypothesis also implies that select types of prostate tumors may be differentially responsive to immune-based strategies and that the clinical stage, pathological grade and underlying genetic landscape may be important criteria in identifying tumors that respond to immune therapies...
July 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28713960/prediction-and-identification-of-b%C3%A2-cell-epitopes-for-tumor-necrosis-factor%C3%A2-%C3%AE
#9
Jun Zhang, Ying Cui, Yinfang Wu, Huiju Wang, Jinjing Ke
The aim of the present study was to predict and identify B‑cell epitopes for mouse tumor necrosis factor‑α (mTNF‑α). DNAStar and BcePred software were used to predict B‑cell epitopes for mTNF‑α. A predicted eight‑branch multiple antigenic polypeptide (MAP) was synthesized and used to immunize BALB/c mice, combined with a promiscuous helper interleukin‑1β epitope (VQGEESNDK, amino acids 163‑171). The serum titer was measured. The specificity and avidity were determined by western blotting and indirect enzyme‑linked immunosorbent assay (ELISA)...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713023/an-extended-mathematical-model-of-tumor-growth-and-its-interaction-with-the-immune-system-to-be-used-for-developing-an-optimized-immunotherapy-treatment-protocol
#10
Milad Qomlaqi, Fariba Bahrami, Maryam Ajami, Jamshid Hajati
BACKGROUND: Chemotherapy is usually known as the main modality for cancer treatment. Nevertheless, most of chronic cancers could not be treated with chemotherapy alone. Immunotherapy is a new modality for cancer treatment that is effective for early stages of cancer and it has fewer side effects compared to chemotherapy, specifically for those types of cancer that are resistant to it. METHOD: This work presents an extended mathematical model to depict interactions between cancerous and adaptive immune system in mouse...
July 14, 2017: Mathematical Biosciences
https://www.readbyqxmd.com/read/28680745/vaccination-targeting-human-her3-alters-the-phenotype-of-infiltrating-t-cells-and-responses-to-immune-checkpoint-inhibition
#11
Takuya Osada, Michael A Morse, Amy Hobeika, Marcio A Diniz, William R Gwin, Zachary Hartman, Junping Wei, Hongtao Guo, Xiao-Yi Yang, Cong-Xiao Liu, Kensuke Kaneko, Gloria Broadwater, H Kim Lyerly
Expression of human epidermal growth factor family member 3 (HER3), a critical heterodimerization partner with EGFR and HER2, promotes more aggressive biology in breast and other epithelial malignancies. As such, inhibiting HER3 could have broad applicability to the treatment of EGFR- and HER2-driven tumors. Although lack of a functional kinase domain limits the use of receptor tyrosine kinase inhibitors, HER3 contains antigenic targets for T cells and antibodies. Using novel human HER3 transgenic mouse models of breast cancer, we demonstrate that immunization with recombinant adenoviral vectors encoding full length human HER3 (Ad-HER3-FL) induces HER3-specific T cells and antibodies, alters the T cell infiltrate in tumors, and influences responses to immune checkpoint inhibitions...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28680744/intratumoral-delivery-of-tumor-antigen-loaded-dc-and-tumor-primed-cd4-t-cells-combined-with-agonist-%C3%AE-gitr-mab-promotes-durable-cd8-t-cell-dependent-antitumor-immunity
#12
Zuqiang Liu, Xingxing Hao, Yi Zhang, Jiying Zhang, Cara D Carey, Louis D Falo, Walter J Storkus, Zhaoyang You
The progressive tumor microenvironment (TME) coordinately supports tumor cell expansion and metastasis, while it antagonizes the survival and (poly-)functionality of antitumor T effector cells. There remains a clear need to develop novel therapeutic strategies that can transform the TME into a pro-inflammatory niche that recruits and sustains protective immune cell populations. While intravenous treatment with tumor-primed CD4(+) T cells combined with intraperitoneal delivery of agonist anti-glucocorticoid-induced TNF receptor (α-GITR) mAb results in objective antitumor responses in murine early stage disease models, this approach is ineffective against more advanced tumors...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28679488/toward-a-new-kind-of-vaccine-a-logical-extension-of-the-symmetrical-immune-network-theory
#13
Reginald Gorczynski, Geoffrey Hoffmann
BACKGROUND: The symmetrical immune network theory, developed in 1975, is based on the existence of specific T cell factors and hypothesizes that normal IgG immune responses comprise the production of 2 kinds of antibodies, namely antigen-specific antibodies and anti-idiotypic antibodies. OBJECTIVE: The aim of this study was to confirm the existence of specific T cells factors and to show that immunization of C3H mice with BL/6 skin or using nominal antigen for immunization (Tetanus Toxoid) induced production of antigen-specific (anti-BL/6 or antitetanus) antibodies plus anti-idiotypic antibodies (C3H anti-anti-C3H)...
July 5, 2017: Interactive Journal of Medical Research
https://www.readbyqxmd.com/read/28675699/immunization-with-a-synthetic-human-muc1-glycopeptide-vaccine-against-tumor-associated-muc1-breaks-tolerance-in-human-muc1-transgenic-mice
#14
Horst Kunz, Natascha Stergiou, Markus Glaffig, Helmut Jonuleit, Edgar Schmitt
Breaking the tolerance is crucial for an effective tumor immunotherapy. We showed that vaccines containing tumor-associated human MUC1 glycopeptides induce strong humoral anti-tumor responses in mice. The question remained whether such vaccines work in humans, in systems where huMUC1 is a self-antigen. To clarify the question, mice transgenic in expressing huMUC1, mimicking the self-tolerant environment, and wild-type mice were vaccinated with a synthetic vaccine. This vaccine comprised STn and Tn antigens bound to a MUC1 tandem repeat peptide coupled to Tetanus Toxoid...
July 4, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28668095/cspg4-a-prototype-oncoantigen-for-translational-immunotherapy-studies
#15
REVIEW
Valeria Rolih, Giuseppina Barutello, Selina Iussich, Raffaella De Maria, Elena Quaglino, Paolo Buracco, Federica Cavallo, Federica Riccardo
Thanks to striking progress in both the understanding of anti-tumor immune response and the characterization of several tumor associated antigens (TAA), a more rational design and more sophisticated strategies for anti-tumor vaccination have been possible. However, the effectiveness of cancer vaccines in clinical trial is still partial, indicating that additional studies are needed to optimize their design and their pre-clinical testing. Indeed, anti-tumor vaccination success relies on the choice of the best TAA to be targeted and on the translational power of the pre-clinical model used to assess its efficacy...
July 1, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28666747/combined-immunotherapy-ctla-4-blockade-potentiates-anti-tumor-response-induced-by-transcutaneous-immunization
#16
Johanna Rausch, Pamela Aranda Lopez, Ariane Bialojan, Mark Denny, Peter Langguth, Hans Christian Probst, Hansjörg Schild, Markus P Radsak
BACKGROUND: The epidermal application of the Toll Like Receptor 7 agonist imiquimod and a T-cell peptide epitope (transcutaneous immunization, TCI) mediates systemic peptide-specific cytotoxic T-cell (CTL) responses and leads to tumor protection in a prophylactic tumor setting. However, it does not accomplish memory formation or permanent defiance of tumors in a therapeutic set-up. As a distinct immunologic approach, CTLA-4 blockade augments systemic immune responses and has shown long-lasting effects in preclinical experiments as well as in clinical trials...
June 16, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28666264/antitumor-immunity-induced-by-ve-cadherin-modified-dc-vaccine
#17
Jing Zhou, Yufeng Xi, Xiyan Mu, Rongce Zhao, Hongdou Chen, Li Zhang, Yang Wu, Qiu Li
Dendritic cells (DCs) are the most potent antigen-presenting cells. A strong interest has been developed in DC vaccines for cancer immunotherapy. Besides, angiogenesis is essential for tumor growth. VE-cadherin has a crucial function in various aspects of vascular biological functions. Here, we produced the full VE-cadherin gene modified DC vaccine (DC-VEC). Its antitumor immunity and chief mechanism driving antitumor effect was evaluated. Analyses were performed including test of antitumor antibody, CTL-mediated cytotoxicity experiment, vascular density, evaluation of the variation of cells and cytokines in immunoregulation...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28660480/dendritic-cell-based-immunotherapy-a-basic-review-and-recent-advances
#18
REVIEW
João Constantino, Célia Gomes, Amílcar Falcão, Bruno Miguel Neves, Maria Teresa Cruz
Dendritic cells (DCs) are considered a very promising arm to activate the immune system in immunotherapeutic strategies against cancer. DCs are the most powerful antigen-presenting cells (APCs), being highly efficient at generating robust immune responses. They are also considered the center of the immune system, since they provide a crucial link between both innate and adaptive immune responses. Thus, DC-based cancer immunotherapy aims to take advantage of these unique characteristics of DCs to better fight cancer...
June 28, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28649380/gitr-ligand-fusion-protein-agonist-enhances-the-tumor-antigen-specific-cd8-t-cell-response-and-leads-to-long-lasting-memory
#19
Nick M Durham, Nick Holoweckyj, Randall S MacGill, Kelly McGlinchey, Ching Ching Leow, Scott H Robbins
BACKGROUND: The expansion of antigen-specific CD8 T cells is important in generating an effective and long-lasting immune response to tumors and viruses. Glucocorticoid-induced tumor necrosis factor receptor family-related receptor (GITR) is a co-stimulatory receptor that binds the GITR ligand (GITRL). Agonism of GITR can produce important signals that drive expansion of effector T cell populations. METHODS: We explored two separate murine tumor models, CT26 and TC-1, for responsiveness to GITR Ligand Fusion Protein(GITRL-FP) monotherapy...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28644608/targeting-cpg-adjuvant-to-lymph-node-via-dextran-conjugate-enhances-antitumor-immunotherapy
#20
Weidong Zhang, Myunggi An, Jingchao Xi, Haipeng Liu
Nucleic acid based adjuvants recognized by Toll-like receptors (TLR) are potent immune system stimulants that can augment the antitumor immune responses in an antigen-specific manner. However, their clinical uses as vaccine adjuvants are limited primarily due to lack of accumulation in the lymph nodes, the anatomic sites where the immune responses are initiated. Here, we showed that chemical conjugation of type B CpG DNA, a TLR9 agonist to dextran polymer dramatically enhanced CpG's lymph node accumulation in mice...
July 6, 2017: Bioconjugate Chemistry
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