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Anti-tumor vaccines

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https://www.readbyqxmd.com/read/28923497/cholera-vaccine-use-is-associated-with-a-reduced-risk-of-death-in-patients-with-colorectal-cancer-a-population-based-study
#1
Jianguang Ji, Jan Sundquist, Kristina Sundquist
BACKGROUND & AIMS: Cholera toxin can act as a modulator of the immune response with anti-inflammatory effects; it reduces development of colon polyps in mouse models of colorectal cancer (CRC). We performed a population-based study to determine whether, in patients with a diagnosis of CRC, subsequent administration of the cholera vaccine (killed Vibrio cholerae O1 whole cells and recombinant cholera toxin B subunit) affects mortality. METHODS: We identified patients from the Swedish Cancer Register who were diagnosed with CRC from July 2005 through December 2012...
September 15, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28923424/depletion-of-regulatory-t-cells-by-anti-icos-antibody-enhances-anti-tumor-immunity-of-tumor-cell-vaccine-in-prostate-cancer
#2
Lijun Mo, Qianmei Chen, Xinji Zhang, Xiaojun Shi, Lili Wei, Dianpeng Zheng, Hongwei Li, Jimin Gao, Jinlong Li, Zhiming Hu
ICOS(+)Treg cells exert important immunosuppressive effects in tumor immunity. We adopt a combination approach of ICOS(+)Treg cells depletion with tumor cell vaccine to evaluate anti-tumor immunity in mouse prostate cancer model. Streptavidin (SA)-mGM-CSF surface-modified RM-1 cells were prepared as the vaccine and the mouse subcutaneous prostate tumor model was used to evaluate the immunity. Tumor growth, flow cytometry, immunohistochemistry, immunofluorescence and enzyme linked immunosorbent assay (ELISA) were performed to evaluate the therapeutic effects...
September 15, 2017: Vaccine
https://www.readbyqxmd.com/read/28923084/viral-based-vaccine-tg4010-induces-broadening-of-specific-immune-response-and-improves-outcome-in-advanced-nsclc
#3
Caroline Tosch, Bérangère Bastien, Luc Barraud, Benoit Grellier, Virginie Nourtier, Murielle Gantzer, Jean Marc Limacher, Eric Quemeneur, Kaïdre Bendjama, Xavier Préville
BACKGROUND: Advanced non-small cell lung cancer patients receiving TG4010, a therapeutic viral vaccine encoding human Mucin 1 and interleukin-2 in addition to standard chemotherapy, displayed longer overall survival in comparison to that of patients treated with standard chemotherapy alone. Our study intended to establish the association between overall survival and vaccine-induced T cell responses against tumor associated antigens (TAA) targeted by the vaccine. METHOD: The TIME trial was a placebo-controlled, randomized phase II study aimed at assessing efficacy of TG4010 with chemotherapy in NSCLC...
September 19, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28920004/targeting-myeloid-derived-suppressor-cells-with-all-trans-retinoic-acid-is-highly-time-dependent-in-therapeutic-tumor-vaccination
#4
Annkristin Heine, Chrystel Flores, Heidrun Gevensleben, Linda Diehl, Mathias Heikenwalder, Marc Ringelhan, Klaus-Peter Janssen, Ulrich Nitsche, Natalio Garbi, Peter Brossart, Percy A Knolle, Christian Kurts, Bastian Höchst
Tumor immune escape is a critical problem which frequently accounts for the failure of therapeutic tumor vaccines. Among the most potent suppressors of tumor immunity are myeloid derived suppressor cells (MDSCs). MDSCs can be targeted by all-trans-retinoic-acid (atRA), which reduced their numbers and increased response rates in several vaccination studies. However, not much is known about the optimal administration interval between atRA and the vaccine as well as about its mode of action. Here we demonstrate in 2 different murine tumor models that mice unresponsive to a therapeutic vaccine harbored higher MDSC numbers than did responders...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919999/first-report-of-clinical-responses-to-immunotherapy-in-3-relapsing-cases-of-chordoma-after-failure-of-standard-therapies
#5
Denis Migliorini, Nicolas Mach, Diego Aguiar, Rémi Vernet, Basile Nicolas Landis, Minerva Becker, Thomas McKee, Valérie Dutoit, Pierre-Yves Dietrich
Chordoma is a rare tumor of notochordal origin, currently principally treated by surgery and/or irradiation. Here, we describe the clinical outcome of 3 consecutive patients with metastatic and locally advanced chordoma, treated with different immunotherapeutic approaches. All patients presented fast growing tumors and failure of standard therapies. One was treated with a tumor-based vaccine, the 2 others with anti-PD1 antibodies, all with impressive clinical and radiological responses. We therefore propose that chordoma is an immunogenic tumor and thus that translational and clinical research is necessary to develop rationally designed immunotherapy approaches...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28905118/administration-of-low-dose-combination-anti-ctla4-anti-cd137-and-anti-ox40-into-murine-tumor-or-proximal-to-the-tumor-draining-lymph-node-induces-systemic-tumor-regression
#6
Jonathan P O Hebb, Adriane R Mosley, Felipe Vences-Catalán, Narendiran Rajasekaran, Anna Rosén, Peter Ellmark, Dean W Felsher
The delivery of immunomodulators directly into the tumor potentially harnesses the existing antigen, tumor-specific infiltrating lymphocytes, and antigen presenting cells. This can confer specificity and generate a potent systemic anti-tumor immune response with lower doses and less toxicity compared to systemic administration, in effect an in situ vaccine. Here, we test this concept using the novel combination of immunomodulators anti-CTLA4, -CD137, and -OX40. The triple combination administered intratumorally at low doses to one tumor of a dual tumor mouse model had dramatic local and systemic anti-tumor efficacy in lymphoma (A20) and solid tumor (MC38) models, consistent with an abscopal effect...
September 13, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28903312/gnp-gapdh1-22-nanovaccines-prevent-neonatal-listeriosis-by-blocking-microglial-apoptosis-and-bacterial-dissemination
#7
Ricardo Calderon-Gonzalez, Elisabet Frande-Cabanes, Hector Teran-Navarro, José María Marimon, Javier Freire, David Salcines-Cuevas, M Carmen Fariñas, Claudia Onzalez-Rico, Marco Marradi, Isabel Garcia, Mirian Alkorta-Gurrutxaga, Aida San Nicolas-Gomez, Ana Castañeda-Sampedro, Sonsoles Yañez-Diaz, Soledad Penades, Carmen Punzon, Javier Gomez-Roman, Fernando Rivera, Manuel Fresno, Carmen Alvarez-Dominguez
Clinical cases of neonatal listeriosis are associated with brain disease and fetal loss due to complications in early or late pregnancy, which suggests that microglial function is altered. This is believed to be the first study to link microglial apoptosis with neonatal listeriosis and listeriosis-associated brain disease, and to propose a new nanovaccine formulation that reverses all effects of listeriosis and confers Listeria monocytogenes (LM)-specific immunity. We examined clinical cases of neonatal listeriosis in 2013-2015 and defined two useful prognostic immune biomarkers to design listeriosis vaccines: high anti-GAPDH1-22 titres and tumor necrosis factor (TNF)/interleukin (IL)-6 ratios...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28895610/cancer-vaccines-using-supramolecular-hydrogels-of-nsaid-modified-peptides-as-adjuvants-abolish-tumorigenesis
#8
Zhongyan Wang, Chunhui Liang, Fang Shi, Tao He, Changyang Gong, Ling Wang, Zhimou Yang
Inflammatory responses play crucial roles in the development and progression of tumors. Tumor-associated inflammation not only promotes tumor growth but also induces the suppression of immune responses against tumors. We demonstrate in this study that hydrogels of nonsteroidal anti-inflammatory drug (NSAID) modified D-tetrapeptides (G(D)F(D)F(D)Y) are promising cancer vaccine adjuvants, especially for Fbp-gel and Car-gel. The hydrogels allow easy incorporation of a protein OVA antigen by vortexing. Our results indicate that vaccines based on Fbp-gel and Car-gel increase IgG production by 1476- and 929-fold, compared with the OVA group, respectively...
September 12, 2017: Nanoscale
https://www.readbyqxmd.com/read/28892469/de-novo-induction-of-intratumoral-lymphoid-structures-and-vessel-normalization-enhances-immunotherapy-in-resistant-tumors
#9
Anna Johansson-Percival, Bo He, Zhi-Jie Li, Alva Kjellén, Karen Russell, Ji Li, Irma Larma, Ruth Ganss
The tumor microenvironment confers profound resistance to anti-cancer immunotherapy. By targeting LIGHT, a member of the TNF superfamily of cytokines, to tumor vessels via a vascular targeting peptide (VTP), we developed a reagent with the dual ability to modulate the angiogenic vasculature and to induce tertiary lymphoid structures (TLSs). LIGHT-VTP triggered the influx of endogenous T cells into autochthonous or syngeneic tumors, which are resistant to immunotherapy. LIGHT-VTP in combination with checkpoint inhibition generated a large number of intratumoral effector and memory T cells with ensuing survival benefits, while the addition of anti-tumor vaccination achieved maximal therapeutic efficacy...
September 11, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28881846/safety-and-efficacy-of-p62-dna-vaccine-elenagen-in-a-first-in-human-trial-in-patients-with-advanced-solid-tumors
#10
Dmitry M Ponomarenko, Irina D Klimova, Yulia A Chapygina, Viktoria V Dvornichenko, Natalia V Zhukova, Rashida V Orlova, Georgy M Manikhas, Alexandr V Zyryanov, Lilya A Burkhanova, Irina I Badrtdinova, Basile N Oshchepkov, Elena V Filippova, Sergei V Orlov, Sergei I Kolesnikov, Albert A Sufianov, Svetlana R Baum, Olga Y Zaitzeva, Andrey B Komissarov, Mikhail P Grudinin, Oleg I Kiselev, Anatoly F Tsyb, Franco Venanzi, Vita Shcherbinina, Andrey Chursov, Vladimir L Gabai, Alexander M Shneider
Elenagen is a plasmid encoding p62/SQSTM1, the first DNA vaccine possessing two mutually complementing mechanisms of action: it elicits immune response against p62 and mitigates systemic chronic inflammation. Previously, Elenagen demonstrated anti-tumor efficacy and safety in rodent tumor models and spontaneous tumors in dogs. This multicenter I/IIa trial evaluated safety and clinical activity of Elenagen in patients with advanced solid tumors. Fifteen patients were treated with escalating doses of Elenagen (1- 5 mg per doses, 5 times weekly) and additional 12 patients received 1 mg dose...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881713/therapeutic-vaccine-to-cure-large-mouse-hepatocellular-carcinomas
#11
Zhen Han, De Yang, Anna Trivett, Joost J Oppenheim
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with limited therapeutic options. Here we report the development of a therapeutic vaccination regimen (shortened as 'TheraVac') consisting of intratumoral delivery of high-mobility group nucleosome-binding protein 1 (HMGN1), R848/resiquimod, and one of the checkpoint inhibitors (e.g. anti-CTLA4, anti-PD-L1, or low dose of Cytoxan). C57BL/6 mice harboring large (approximately 1 cm in diameter) established subcutaneous Hepa1-6 hepatomas were cured by intratumoral injections of TheraVac and became tumor-free long-term survivors...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881671/malignant-pericytes-expressing-gt198-give-rise-to-tumor-cells-through-angiogenesis
#12
Liyong Zhang, Yan Wang, Mohammad H Rashid, Min Liu, Kartik Angara, Nahid F Mivechi, Nita J Maihle, Ali S Arbab, Lan Ko
Angiogenesis promotes tumor development. Understanding the crucial factors regulating tumor angiogenesis may reveal new therapeutic targets. Human GT198 (PSMC3IP or Hop2) is an oncoprotein encoded by a DNA repair gene that is overexpressed in tumor stromal vasculature to stimulate the expression of angiogenic factors. Here we show that pericytes expressing GT198 give rise to tumor cells through angiogenesis. GT198(+) pericytes and perivascular cells are commonly present in the stromal compartment of various human solid tumors and rodent xenograft tumor models...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28867165/antitumor-antibodies-can-drive-therapeutic-t-cell-responses
#13
REVIEW
K Dane Wittrup
The classical view of therapeutic monoclonal antibodies (mAbs) against tumor-associated antigens (TAAs) is that their mechanism of action is dominated by signal blocking or the cytotoxicity of Fc-driven innate immune effector functions. We review here a mounting body of evidence that anti-TAA mAbs are capable of profoundly synergizing with T cell-directed immunotherapies such as checkpoint blockade and adoptive cell therapy. Two key components account for this synergy: (i) a self-vaccinal effect mediated by dendritic cells (DCs); and (ii) an inflammatory repolarization of the tumor microenvironment...
September 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28865999/a-novel-vaccine-targeting-glypican-3-as-a-treatment-for-hepatocellular-carcinoma
#14
Qunfeng Wu, Liya Pi, Thu Le Trinh, Chaohui Zuo, Man Xia, Yu Jiao, Zhouhua Hou, Sung Jo, William Puszyk, Kien Pham, David R Nelson, Keith Robertson, David Ostrov, Pranela Rameshwar, Chang Qing Xia, Chen Liu
Hepatocellular carcinoma (HCC) has a high morbidity and mortality rate worldwide, with limited treatment options. Glypican-3 (GPC3) is a glycosylphosphatidylinositol-anchored glycoprotein that is overexpressed in most HCC tissues but not in normal tissues. GPC3-targeting antibody therapy shows limited response in a clinical trial due to the lack of a tumor-specific cytotoxic T lymphocyte (CTL) response. Here, in C57/B6 mice, we demonstrated that intravenous infusion of GPC3-coupled lymphocytes (LC/GPC3(+)) elicited robust GPC3-specific antibody and CTL responses, which effectively restricted proliferation and lysed cultured-HCC cells...
August 10, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28855903/impact-of-depleting-therapeutic-monoclonal-antibodies-on-the-host-adaptive-immunity-a-bonus-or-a-malus
#15
REVIEW
Claire Deligne, Benoît Milcent, Nathalie Josseaume, Jean-Luc Teillaud, Sophie Sibéril
Clinical responses to anti-tumor monoclonal antibody (mAb) treatment have been regarded for many years only as a consequence of the ability of mAbs to destroy tumor cells by innate immune effector mechanisms. More recently, it has also been shown that anti-tumor antibodies can induce a long-lasting anti-tumor adaptive immunity, likely responsible for durable clinical responses, a phenomenon that has been termed the vaccinal effect of antibodies. However, some of these anti-tumor antibodies are directed against molecules expressed both by tumor cells and normal immune cells, in particular lymphocytes, and, hence, can also strongly affect the host adaptive immunity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28854279/transfer-of-in-vitro-expanded-na%C3%A3-ve-t-cells-after-lymphodepletion-enhances-antitumor-immunity-through-the-induction-of-polyclonal-antitumor-effector-t-cells
#16
Tomohiro Tanaka, Satoshi Watanabe, Miho Takahashi, Ko Sato, Yu Saida, Junko Baba, Masashi Arita, Miyuki Sato, Aya Ohtsubo, Satoshi Shoji, Koichiro Nozaki, Kosuke Ichikawa, Rie Kondo, Nobumasa Aoki, Yasuyoshi Ohshima, Takuro Sakagami, Tetsuya Abe, Hiroshi Moro, Toshiyuki Koya, Junta Tanaka, Hiroshi Kagamu, Hirohisa Yoshizawa, Toshiaki Kikuchi
The adoptive transfer of effector T cells combined with lymphodepletion has demonstrated promising antitumor effects in mice and humans, although the availability of tumor-specific T cells is limited. We and others have also demonstrated that the transfer of polyclonal naïve T cells induces tumor-specific effector T cells and enhances antitumor immunity after lymphodepletion. Because tumors have been demonstrated to induce immunosuppressive networks and regulate the function of T cells, obtaining a sufficient number of fully functional naïve T cells that are able to differentiate into tumor-specific effector T cells remains difficult...
2017: PloS One
https://www.readbyqxmd.com/read/28845889/heterovalent-glycodendrimers-as-epitope-carriers-for-antitumoral-synthetic-vaccines
#17
Carlo Pifferi, Baptiste Thomas, David Goyard, Nathalie Berthet, Olivier Renaudet
The large majority of TACA-based antitumoral vaccines targets only one carbohydrate antigen, thereby often resulting in the incomplete destruction of cancer cells. However, the morphological heterogeneity of the tumor glycocalix, which is in constant evolution during malignant transformation, is a crucial point to consider in the design of vaccine candidates. In this paper, we report an efficient synthetic strategy based on orthogonal chemoselective ligations to prepare fully synthetic glycosylated cyclopeptide scaffolds grafted with both Tn and TF antigen analogues...
August 28, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28838413/sexuality-fertility-and-pregnancy-in-crohn-s-disease
#18
REVIEW
Jill K J Gaidos, Sunanda V Kane
Many factors influence the sexual health of people with Crohn's disease, but active disease and depression play key roles. The fertility rate in nonoperated patients with inflammatory bowel disease with quiescent disease is similar to that in the general population. Crohn's disease can increase the risk for adverse pregnancy outcomes, but being in remission on a stable, steroid-free medication regimen for at least 3 months before conception and adhering to the treatment throughout pregnancy can improve outcomes...
September 2017: Gastroenterology Clinics of North America
https://www.readbyqxmd.com/read/28836068/rates-and-predictors-of-vaccinations-among-inflammatory-bowel-disease-patients-receiving-anti-tumor-necrosis-factor-agents
#19
Hung-Viet Pham, Imran Hasan, Natalia Udaltsova, Kathy Pham, Oren Abramson, Mary Anne Armstrong, Debbie Postlethwaite, Dan Li
BACKGROUND: As an important quality measure, the rates of recommended immunizations among immunocompromised inflammatory bowel disease (IBD) patients in community practice have not been well studied. AIMS: This study sought to investigate the rates and predictors of recommended immunizations and screening tests among IBD patients receiving anti-tumor necrosis factor (TNF) therapy in a large integrated healthcare organization. METHODS: We conducted a retrospective cohort study of 1401 IBD patients on anti-TNF therapy between 2010 and 2013 within the Kaiser Permanente Northern California healthcare system...
August 23, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28830889/dendritic-cell-vaccination-as-post-remission-treatment-to-prevent-or-delay-relapse-in-acute-myeloid-leukemia
#20
Sébastien Anguille, Ann L Van de Velde, Evelien L Smits, Viggo F Van Tendeloo, Gunnar Juliusson, Nathalie Cools, Griet Nijs, Barbara Stein, Eva Lion, Ann Van Driessche, Irma Vandenbosch, Anke Verlinden, Alain P Gadisseur, Wilfried A Schroyens, Ludo Muylle, Katrien Vermeulen, Marie-Berthe Maes, Kathleen Deiteren, Ronald Malfait, Emma Gostick, Martin Lammens, Marie M Couttenye, Philippe Jorens, Herman Goossens, David A Price, Kristin Ladell, Yoshihiro Oka, Fumihiro Fujiki, Yusuke Oji, Haruo Sugiyama, Zwi N Berneman
Relapse is a major problem in acute myeloid leukemia (AML) and adversely impacts survival. In this phase II study, we investigated the effect of vaccination with dendritic cells (DCs) electroporated with Wilms' tumor 1 (WT1) mRNA as post-remission treatment in 30 AML patients at very high risk of relapse. There was a demonstrable anti-leukemic response in 13 patients. Nine patients achieved molecular remission as demonstrated by normalization of WT1 transcript levels, 5 of which are sustained after a median follow-up of 109...
August 22, 2017: Blood
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