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Anti-tumor vaccines

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https://www.readbyqxmd.com/read/28539888/safety-and-immunogenicity-of-a-human-epidermal-growth-factor-receptor-1-her1-based-vaccine-in-prostate-castration-resistant-carcinoma-patients-a-dose-escalation-phase-i-study-trial
#1
Iraida Caballero, Lazaro E Aira, Anabel Lavastida, Xitlally Popa, Javier Rivero, Joaquín González, Mónica Mesa, Narjara González, Kelly Coba, Patricia Lorenzo-Luaces, Barbara Wilkinson, Yuliannis Santiesteban, Yanela Santiesteban, Mayelin Troche, Eduardo Suarez, Tania Crombet, Belinda Sánchez, Angel Casacó, Amparo Macías, Zaima Mazorra
Metastatic castration-resistant prostate cancer (CRPC) remains incurable due to the lack of effective therapies. Activation of the human epidermal growth factor receptor 1 (HER1) in prostate cancer contributes to metastatic progression as well as to disease relapse. Here, we determined the toxicity and immunogenicity of a HER1-based cancer vaccine in CRPC patients included in a phase I clinical trial. CRPC patients (n = 24) were intramuscularly vaccinated with HER1 vaccine consisting of the extracellular domain of HER1 molecule (ECD) and very small size proteoliposome from Neisseria meningitidis (VSSP) and Montanide ISA-51 VG as adjuvants...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28539528/prospect-of-immunotherapy-for-glioblastoma-tumor-vaccine-immune-checkpoint-inhibitors-and-combination-therapy
#2
Eiichi Ishikawa, Tetsuya Yamamoto, Akira Matsumura
To date, clinical trials of various vaccine therapies using autologous tumor antigens or tumor-associated/specific antigen peptide with adjuvants have been performed to treat patients with high-grade gliomas (HGG). Furthermore, immune checkpoint pathway-targeted therapies including anti- programmed cell death 1 (PD-1) antibody have been remarkably effective in other neoplasms, and various clinical trials with anti-PD-1 antibody in patients with HGG have started to date. It is possible that up-regulation of immune checkpoint molecules in tumor tissues after vaccine therapy may be one of the mechanisms of vaccine failure...
May 24, 2017: Neurologia Medico-chirurgica
https://www.readbyqxmd.com/read/28538872/melanoma-tumor-microenvironment-and-new-treatments
#3
Mara Huffenbaecher Giavina-Bianchi, Pedro Francisco Giavina-Bianchi, Cyro Festa
In the recent past years, many discoveries in the tumor microenvironment have led to changes in the management of melanoma and it is rising up hopes, specially, to those in advanced stages. FDA approved seven new drugs from 2011 to 2014. They are: Vemurafenib, Dabrafenib and Trametinib, kinases inhibitors used for patients that have BRAFV600E mutation; Ipilimumab (anti-CTLA4), Pembrolizumab (anti-PD-1) and Nivolumab (anti-PD-1), monoclonal antibodies that stimulate the immune system; and Peginterferon alfa-2b, an anti-proliferative cytokine used as adjuvant therapy...
March 2017: Anais Brasileiros de Dermatologia
https://www.readbyqxmd.com/read/28537884/a-cancer-vaccine-based-on-fluorine-modified-sialyl-tn-induces-robust-immune-responses-in-a-murine-model
#4
Chengcheng Song, Xiu-Jing Zheng, Chang-Cheng Liu, Yifa Zhou, Xin-Shan Ye
Development of an effective vaccine to target tumor associated carbohydrate antigens, aberrantly expressed on the cell surface of various carcinomas, is an appealing approach toward cancer immunotherapy. However, a major problem of carbohydrate antigens is their poor immunogenicity. Immunization with modified-carbohydrate antigens could improve the immunogenicity and induce cross reaction with the native carbohydrate antigens. In this study, we investigated the antitumor ability of three fluoro-substituted sialyl-Tn (STn) analogues (2, 3, 4) coupled to KLH (keyhole limpet hemocyanin) and studied the mechanism of tumor immunotherapy of the vaccines in a murine model of colon cancer...
May 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28536351/oncolytic-vesicular-stomatitis-virus-as-a-viro-immunotherapy-defeating-cancer-with-a-hammer-and-anvil
#5
REVIEW
Michael Karl Melzer, Arturo Lopez-Martinez, Jennifer Altomonte
Oncolytic viruses have gained much attention in recent years, due, not only to their ability to selectively replicate in and lyse tumor cells, but to their potential to stimulate antitumor immune responses directed against the tumor. Vesicular stomatitis virus (VSV), a negative-strand RNA virus, is under intense development as an oncolytic virus due to a variety of favorable properties, including its rapid replication kinetics, inherent tumor specificity, and its potential to elicit a broad range of immunomodulatory responses to break immune tolerance in the tumor microenvironment...
February 10, 2017: Biomedicines
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
#6
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/28536029/specific-humoral-and-cellular-immune-responses-in-cancer-patients-undergoing-chronic-immunization-with-a-vegf-based-therapeutic-vaccine
#7
Yanelys Morera, Javier Sánchez, Mónica Bequet-Romero, Katty-Hind Selman-Housein, Ana de la Torre, Francisco Hernández-Bernal, Yenima Martín, Acralys Garabito, Jesús Piñero, Cimara Bermúdez, Josué de la Torre, Marta Ayala, Jorge V Gavilondo
CIGB-247 is a cancer therapeutic vaccine, based on recombinant modified human vascular endothelial growth factor (VEGF) as antigen, in combination with the adjuvant VSSP, a bacterially-derived adjuvant. The vaccine have demonstrated efficacy in several murine malignancy models. These studies supported the rationale for a phase I clinical trial where safety, tolerance, and immunogenicity of CIGB-247 was studied in patients with advanced solid tumors at three antigen dose level. Surviving individuals of this clinical trial were eligible to receive off-trial voluntary re-immunizations...
May 20, 2017: Vaccine
https://www.readbyqxmd.com/read/28531117/immunobiology-of-newcastle-disease-virus-and-its-use-for-prophylactic-vaccination-in-poultry-and-as-adjuvant-for-therapeutic-vaccination-in-cancer-patients
#8
REVIEW
Volker Schirrmacher
Newcastle disease (ND) is one of the most important diseases of poultry worldwide. In the last decades, molecular research has gained a lot of new information about its causative agent, newcastledisease virus (NDV). In poultry industry, certain strains of NDV have been used for preventive vaccination for more than 60 years. NDV has also been applied to cancer patients with beneficial effects for about 50 years, but this is less well known. The molecular basis for these differential effects of NDV in birds and man have been elucidated in the last decades and are explained in this review...
May 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28529901/combining-immunotherapy-and-radiation-therapy-for-small-cell-lung-cancer-and-thymic-tumors
#9
REVIEW
Suchit H Patel, Andreas Rimner, Roger B Cohen
Recent work with immunotherapy has shown promising results with treatment of several solid malignancies, and there are several reports of good systemic responses with the combination of immunotherapy and radiation therapy (RT), most notably in advanced melanoma. Given the rapid increase in the use of checkpoint blockade as well as anti-tumor vaccines, we review here the preclinical rationale and ongoing clinical work in combining immunotherapy with RT for small cell lung cancer (SCLC) and thymic tumors. While there are several reports of promising results with the combination of immunotherapy and conventional systemic treatment, we focus here on the ongoing clinical studies that combine immunotherapy with RT, and highlight the emerging data for this multimodality approach as well as key preclinical and clinical issues that remain to be addressed...
April 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28521477/t-cell-immunity-induced-by-a-bivalent-salmonella-based-ceacam6-and-4-1bbl-vaccines-in-a-rat-colorectal-cancer-model
#10
Chunhui Jin, Xiaoqing Duan, Yingying Liu, Jianhong Zhu, Ke Zhang, Yuanting Zhang, Tingting Xia, Yajun Fei, Jianxin Ye
The present study investigated the anti-tumor mechanisms of recombinant non-specific cross-reacting antigen (CEACAM6) and 4-1BB ligand (4-1BBL) Salmonella-based vaccines, and the effect that these vaccinations have on memory T cells and T helper (Th) cell polarization. Colon tumors were induced in rats via 1,2-dimethylhydrazine (DMH) injections. Rats were then treated with injections of attenuated Salmonella typhimurium carrying pIRES-CEACAM6, pIRES-4-1BBL or pIRES-CEACAM6-4-1BBL. In total, 4 vaccine injections, one every other week, were administered during the 8 weeks subsequent to the DMH injection...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28515346/the-novel-complex-combination-of-alum-cpg-odn-and-hh2-as-adjuvant-in-cancer-vaccine-effectively-suppresses-tumor-growth-in-vivo
#11
Yaomei Tian, Meng Li, Chaoheng Yu, Rui Zhang, Xueyan Zhang, Rong Huang, Lian Lu, Fengjiao Yuan, Yingzi Fan, Bailing Zhou, Ke Men, Heng Xu, Li Yang
Single-component adjuvant is prone to eliciting a specific type of Th1 or Th2 response. So, the development of combinatorial adjuvants inducing a robust mixed Th1/Th2 response is a promising vaccination strategy against cancer. Here, we describe a novel combination of aluminum salts (alum), CpG oligodeoxynucleotide (CpG) and innate defense regulator peptide HH2 for improving anti-tumor immune responses. The CpG-HH2 complex significantly enhanced the production of IFN-γ, TNF-α and IL-1β, promoted the uptake of antigen and strengthened the activation of p38, Erk1/2 and NF-κB in vitro, compared to CpG or HH2 alone...
April 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28507792/oncolytic-measles-virus-encoding-interleukin-12-mediates-potent-antitumor-effects-through-t-cell-activation
#12
Rūta Veinalde, Christian Grossardt, Laura Hartmann, Marie-Claude Bourgeois-Daigneault, John C Bell, Dirk Jäger, Christof von Kalle, Guy Ungerechts, Christine E Engeland
Combination of oncolytic virotherapy with immunomodulators is emerging as a promising therapeutic strategy for numerous tumor entities. In this study, we developed measles Schwarz vaccine strain vectors encoding immunomodulators to support different phases in the establishment of antitumor immune responses. Therapeutic efficacy of the novel vectors was evaluated in the immunocompetent MC38cea tumor model. We identified vectors encoding an IL-12 fusion protein (MeVac FmIL-12) and an antibody against PD-L1 (MeVac anti-PD-L1), respectively, as the most effective...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28494274/personalized-t-cell-mediated-cancer-immunotherapy-progress-and-challenges
#13
REVIEW
Michael T Bethune, Alok V Joglekar
Immunotherapies are yielding effective treatments for several previously untreatable cancers. Until recently, vaccines and adoptive cell therapies have been designed to target public tumor antigens common to multiple patients rather than private antigens specific to a single patient. Due to the difficulty of identifying public antigens that are expressed exclusively on tumor cells, these studies have yielded both clinical successes and serious immune-related adverse events. Multiple avenues of research now underscore the centrality of tumor-specific mutated private antigens to endogenous anti-tumor immunity...
May 8, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28492521/coinjection-of-il2-dna-enhances-e7-specific-antitumor-immunity-elicited-by-intravaginal-therapeutic-hpv-dna-vaccination-with-electroporation
#14
Y Sun, S Peng, A Yang, E Farmer, T-C Wu, Chien-Fu Hung
The generation and use of therapeutic human papillomavirus (HPV) DNA vaccines represent an appealing treatment method against HPV-associated cervical cancer due to their safety and durability. Previously, we created a therapeutic HPV DNA vaccine candidate by linking the HPV16-E7 DNA sequence to calreticulin (CRT/E7), which we showed could generate significant E7-specific cytotoxic T lymphocyte (CTL)-mediated anti-tumor immune responses against HPV16 oncogenes expressing murine tumor model TC-1. Here we assess the therapeutic efficacy of intravaginal immunization with pcDNA3-CRT/E7 followed by electroporation...
May 11, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28480306/dendritic-cell-therapies-for-hematologic-malignancies
#15
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/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
#16
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/28464762/cancer-targeted-oncolytic-adenoviruses-for-modulation-of-the-immune-system
#17
Vincenzo Cerullo, Cristian Capasso, Markus Vähä-Koskela, Otto Hemminki, Akseli Hemminki
Adenovirus is one of the most commonly used vectors for gene therapy and it is the first approved virus-derived drug for treatment of cancer. As an oncolytic agent, it can induce lysis of infected cells, but it can also engage the immune system, promoting activation and maturation of antigen-presenting cells (APCs). In essence, oncolysis combined with the associated immunostimulatory actions result in a "personalized in situ vaccine" for each patient. In order to take full advantage of these features, we should try to understand how adenovirus interacts with the immune system, what are the receptors involved in triggering subsequent signals and which kind of responses they elicit...
May 2, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28460617/impact-of-il-12-in-cancer
#18
Xinjie Lu
BACKGROUND: Interleukin 12 (IL-12) is a pleiotropic cytokine that plays an essential role in Th1-type immune response against cancer, a condition where cells in a particular part of the body grow and reproduce uncontrollably. METHODS: In this review, we describe the structural features of IL-12 family and their roles involved in cancer. RESULTS: IL-12 has been demonstrated to regulate both innate (natural killer cells) and adaptive (cytotoxic T lymphocytes) immunities in cancer therapy...
April 26, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28457885/genome-engineering-of-stem-cells-for-autonomously-regulated-closed-loop-delivery-of-biologic-drugs
#19
Jonathan M Brunger, Ananya Zutshi, Vincent P Willard, Charles A Gersbach, Farshid Guilak
Chronic inflammatory diseases such as arthritis are characterized by dysregulated responses to pro-inflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor α (TNF-α). Pharmacologic anti-cytokine therapies are often effective at diminishing this inflammatory response but have significant side effects and are used at high, constant doses that do not reflect the dynamic nature of disease activity. Using the CRISPR/Cas9 genome-engineering system, we created stem cells that antagonize IL-1- or TNF-α-mediated inflammation in an autoregulated, feedback-controlled manner...
May 9, 2017: Stem Cell Reports
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
#20
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
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