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Anti-tumor vaccines

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https://www.readbyqxmd.com/read/29329556/cancer-immunotherapy-beyond-immune-checkpoint-inhibitors
#1
REVIEW
Julian A Marin-Acevedo, Aixa E Soyano, Bhagirathbhai Dholaria, Keith L Knutson, Yanyan Lou
Malignant cells have the capacity to rapidly grow exponentially and spread in part by suppressing, evading, and exploiting the host immune system. Immunotherapy is a form of oncologic treatment directed towards enhancing the host immune system against cancer. In recent years, manipulation of immune checkpoints or pathways has emerged as an important and effective form of immunotherapy. Agents that target cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1 (PD-L1) are the most widely studied and recognized...
January 12, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29322496/wt1-peptide-based-immunotherapy-for-advanced-thymic-epithelial-malignancies
#2
Yusuke Oji, Masayoshi Inoue, Yoshito Takeda, Naoki Hosen, Yasushi Shintani, Manabu Kawakami, Takuya Harada, Yui Murakami, Miki Iwai, Mari Fukuda, Sumiyuki Nishida, Jun Nakata, Yoshiki Nakae, Satoshi Takashima, Toshiaki Shirakata, Hiroko Nakajima, Kana Hasegawa, Hiroshi Kida, Takashi Kijima, Soyoko Morimoto, Fumihiro Fujiki, Akihiro Tsuboi, Eiichi Morii, Satoshi Morita, Junichi Sakamoto, Atsushi Kumanogoh, Yoshihiro Oka, Meinoshin Okumura, Haruo Sugiyama
Thymic epithelial tumors are rare malignancies, and no optimal therapeutic regimen has been defined for patients with advanced disease. Patients with advanced thymic epithelial tumors, which were resistant or intolerable to prior therapies, were eligible for this study. Patients received 9 mer-WT1-derived peptide emulsified with Montanide ISA51 adjuvant via intradermal administration once a week as a monotherapy. After the 3 month-protocol treatment, the treatment was continued mostly at intervals of 2 to 4 weeks until disease progression or intolerable adverse events occurred...
January 11, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29320562/m1-like-macrophages-change-tumor-blood-vessels-and-microenvironment-in-murine-melanoma
#3
Magdalena Jarosz-Biej, Natalia Kamińska, Sybilla Matuszczak, Tomasz Cichoń, Jolanta Pamuła-Piłat, Justyna Czapla, Ryszard Smolarczyk, Daria Skwarzyńska, Klaudia Kulik, Stanisław Szala
Tumor-associated macrophages (TAMs) play a significant role in at least two key processes underlying neoplastic progression: angiogenesis and immune surveillance. TAMs phenotypic changes play important role in tumor vessel abnormalization/ normalization. M2-like TAMs stimulate immunosuppression and formation of defective tumor blood vessels leading to tumor progression. In contrast M1-like TAMs trigger immune response and normalize irregular tumor vascular network which should sensitize cancer cells to chemo- and radiotherapy and lead to tumor growth regression...
2018: PloS One
https://www.readbyqxmd.com/read/29316610/development-of-a-deimmunized-bispecific-immunotoxin-ddt2219-against-b-cell-malignancies
#4
Joerg U Schmohl, Deborah Todhunter, Elizabeth Taras, Veronika Bachanova, Daniel A Vallera
Diphtheria toxin (DT) related targeted toxins are effective in cancer treatment, but efficacy diminishes in time because of their immunogenic potential and/or former vaccinations. In order to overcome this limitation for DT2219, a promising bispecific targeted toxin which targets CD19 and CD22, we deimmunized the DT moiety, and thereby developed an exciting improved drug (dDT2219) which still has the potential to sufficiently target B-cell malignancies but also limits clearance because of its reduced immunogenicity...
January 6, 2018: Toxins
https://www.readbyqxmd.com/read/29316037/development-of-a-recombinant-murine-tumor-model-using-hepatoma-cells-expressing-hepatitis-c-virus-hcv-non-structural-antigens
#5
K Young, K Haq, S MacLean, R Dudani, S M Elahi, R Gilbert, R Weeratna, L Krishnan
Hepatitis C virus (HCV) chronically infects 2-3% of the world's population, causing liver disease and cancer with prolonged infection. The narrow host range of the virus, being restricted largely to human hepatocytes, has made the development of a relevant infection and reliable model to evaluate the efficacy of vaccines a challenge. We have developed a novel approach to accomplish this by generating a murine hepatoma cell line stably expressing non-structural HCV antigens which can be used in vitro or in vivo to test HCV vaccine efficacies...
January 6, 2018: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29313971/in-vivo-antitumor-function-of-tumor-antigen-specific-ctls-generated-in-the-presence-of-ox40-co-stimulation-in-vitro
#6
Ngoc Pham Minh, Satoshi Murata, Naomi Kitamura, Tomoyuki Ueki, Masatsugu Kojima, Toru Miyake, Katsushi Takebayashi, Hirokazu Kodama, Eiji Mekata, Masaji Tani
Adoptive cell transfer (ACT) is an emerging and promising cancer immunotherapy that has been improved through various approaches. Here, we described the distinctive characteristics and functions of tumor Ag-specific effector CD8+ T-cells, co-cultured with a tumor specific peptide and a stimulatory anti-OX40 antibody, before being used for ACT therapy in tumor-bearing mouse recipients. Splenic T-cells were obtained from wild-type FVB/N mice that had been injected with a HER2/neu (neu)-expressing tumor and a neu-vaccine...
January 4, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29312597/targeting-of-cd122-enhances-antitumor-immunity-by-altering-the-tumor-immune-environment
#7
Daniel O Villarreal, Michael J Allegrezza, Melissa A Smith, Diana Chin, Leopoldo L Luistro, Linda A Snyder
Mounting evidence demonstrates that CD8+CD122+ T cells have suppressive properties with the capacity to inhibit T cell responses. Therefore, these cells are rational targets for cancer immunotherapy. Here, we demonstrate that CD122 monoclonal antibody (mAb; aCD122) therapy significantly suppressed tumor growth and improved long-term survival in tumor-bearing mice. This therapeutic effect correlated with enhanced polyfunctional, cytolytic intratumoral CD8+ T cells and a decrease in granulocytic myeloid-derived suppressor cells (G-MDSCs)...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29311431/evaluation-of-ph-sensitive-fusogenic-polymer-modified-liposomes-co-loaded-with-antigen-and-%C3%AE-galactosylceramide-as-an-anti-tumor-vaccine
#8
Seiji Okazaki, Tadashi Iwasaki, Eiji Yuba, Shinobu Watarai
pH-Sensitive fusogenic polymer-modified (pH-sensitive) liposomes co-loaded with tumor model antigen, ovalbumin (OVA), and adjuvant, α-galactosylceramide (α-GalCer) were fabricated and administered subcutaneously into mice. The ability of pH-sensitive liposomes containing OVA and α-GalCer to stimulate cellular and humoral immune responses in vivo was compared with OVA-encapsulating pH-sensitive liposomes as well as with OVA alone. After immunization, significant OVA-specific antibodies were detected in the serum...
December 28, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/29305519/antigen-specific-antitumor-responses-induced-by-ox40-agonist-are-enhanced-by-ido-inhibitor-indoximod
#9
Zuzana Berrong, Mikayel Mkrtichyan, Shamim Ahmad, Mason Webb, Eslam Mohamed, Grigori Okoev, Adelaida Matevosyan, Rajeev Shrimali, Rasha Abu Eid, Scott Hammond, John E Janik, Samir N Khleif
Although an immune response to tumors may be generated using vaccines, so far, this approach has only shown minimal clinical success. This is attributed to the tendency of cancer to escape immune surveillance via multiple immune suppressive mechanisms. Successful cancer immunotherapy requires targeting these inhibitory mechanisms along with enhancement of antigen-specific immune responses to promote sustained tumor-specific immunity. Here we evaluated the effect of indoximod, an inhibitor of the immunosuppressive indoleamine-(2,3)-dioxygenase (IDO) pathway, on antitumor efficacy of anti-OX40 agonist in the context of vaccine in the IDO- TC-1 tumor model...
January 5, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29301826/p53-reactive-t-cells-are-associated-with-clinical-benefit-in-patients-with-platinum-resistant-epithelial-ovarian-cancer-after-treatment-with-a-p53-vaccine-and-gemcitabine-chemotherapy
#10
Nicola R Hardwick, Paul Frankel, Christopher Ruel, Julie Kilpatrick, Weimin Tsai, Ferdynand Kos, Teodora I Kaltcheva, Lucille Leong, Robert Morgan, Vincent Chung, Raechelle Tinsley, Melissa Eng, Sharon P Wilczynski, Joshua D I Ellenhorn, Don J Diamond, Mihaela Cristea
PURPOSE: To conduct a Phase I trial of a Modified Vaccinia Ankara vaccine delivering wild type human p53 (p53MVA) in combination with gemcitabine chemotherapy in patients with platinum-resistant ovarian cancer. EXPERIMENTAL DESIGN: Patients received gemcitabine on days 1 and 8 and p53MVA vaccine on day 15, during the first 3 cycles of chemotherapy. Toxicity was classified using the NCI Common Toxicity Criteria and clinical response assessed by CT scan. Peripheral blood samples were collected for immunophenotyping and monitoring of anti-p53 immune responses...
January 4, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29298343/epcam-peptide-primed-dendritic-cell-vaccination-confers-significant-anti-tumor-immunity-in-hepatocellular-carcinoma-cells
#11
Yoo Jin Choi, Seong-Joon Park, You-Soo Park, Hee Sung Park, Kwang Mo Yang, Kyu Heo
Cancer stem-like cells (CSCs) may play a key role in tumor initiation, self-renewal, differentiation, and resistance to current treatments. Dendritic cells (DCs) play a vital role in host immune reactions as well as antigen presentation. In this study, we explored the suitability of using CSC peptides as antigen sources for DC vaccination against human breast cancer and hepatocellular carcinoma (HCC) with the aim of achieving CSC targeting and enhancing anti-tumor immunity. CD44 is used as a CSC marker for breast cancer and EpCAM is used as a CSC marker for HCC...
2018: PloS One
https://www.readbyqxmd.com/read/29285934/synthetic-polymeric-mixed-micelles-target-to-lymph-node-triggering-enhanced-cellular-and-humoral-immune-responses
#12
Chenxi Li, Xiaoxu Zhang, Qing Chen, Jiulong Zhang, Wenpan Li, Haiyang Hu, Xiuli Zhao, Mingxi Qiao, Dawei Chen
It has been widely accepted that lymph nodes (LNs) are critical targets of cancer vaccines since antigen presentation and initiation of T cell-mediated immune responses occur primarily at these locations. In this study, amphiphilic diblock copolymer PEOz-PLA combined with carboxylterminalted-Pluronic F127 were used to construct mixed micelles (carboxylated-NPs) for co-delivery of antigen OVA and Toll-like receptor-7 agonist CL264 (carboxylated-NPs/OVA/CL264) to the LN resident DCs. The results showed that the small, sub-60nm size of the self-assembled mixed micelles enables them to rapidly penetrate into lymphatic vessels and reach DLNs after subcutaneous injection...
December 29, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29285731/therapeutic-cancer-vaccines-how-much-closer-are-we
#13
Douglas G McNeel
The promise of immune-based therapies to treat cancer has been realized over the last several years with several breakthrough therapies, including T-cell checkpoint inhibitors and chimeric antigen receptor (CAR)-T cell therapies. While cancer vaccines have been investigated for many decades, to date only one has been approved in the USA as a treatment for existing cancer. The failure of several anti-tumor vaccines in large phase III trials has led many to question their future role in cancer treatment. Trials to date have demonstrated that many cancer vaccines can elicit tumor-specific T cells, but these T cells may be insufficient to mediate substantial anti-tumor effects without concurrent blockade of tumor-resistance mechanisms...
December 28, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/29277666/assessment-of-in-vivo-anti-tumor-activity-of-human-umbilical-vein-endothelial-cell-vaccines-prepared-by-various-antigen-forms
#14
Ling Zhou, Chunfeng Si, Defang Li, Meiyu Lu, Weilan Zhong, Zeping Xie, Lin Guo, Shumin Zhang, Maolei Xu
Human umbilical vein endothelial cell (HUVEC) vaccine has been proved as an effective whole-cell vaccine, but the modest therapeutic anti-tumor efficiency limits its clinical use. Various antigen forms, including paraformaldehyde-fixed HUVEC, glutaraldehyde-fixed HUVEC, HUVEC lysate and live HUVEC, have been intensively used in HUVEC vaccine preparation, however, the most effective antigen form has not yet been identified. In the present study, these four commonly used antigen forms were used to prepare vaccines named Para-Fixed-EC, Glu-Fixed-EC, Lysate-EC, and Live-EC respectively, and the anti-tumor efficacy of these four vaccines was investigated...
December 22, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29275473/immunotherapeutic-targeting-of-tumor-associated-blood-vessels
#15
Kellsye L Fabian, Walter J Storkus
Pathological angiogenesis occurs during tumor progression and leads in the formation of an abnormal vasculature in the tumor microenvironment (TME). The tumor vasculature is disorganized, tortuous and leaky, resulting in high interstitial pressure and hypoxia in the TME, all of which are events that support tumor growth and survival. Given the sustaining role of the tumor vasculature, it has become an increasingly attractive target for the development of anti-cancer therapies. Antibodies, tyrosine kinase inhibitors and cancer vaccines that target pro-angiogenic factors, angiogenesis-associated receptors or tumor blood vessel-associated antigens continue to be developed and tested for therapeutic efficacy...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29275464/the-role-of-tumor-microenvironment-in-cancer-immunotherapy
#16
Timothy Frankel, Mirna Perusina Lanfranca, Weiping Zou
The field of tumor immunology and immunotherapy has undergone a renaissance in the past decade do in large part to a better understanding of the tumor immune microenvironment. After suffering countless successes and setbacks in the twentieth century, immunotherapy has now come to the forefront of cancer research and is recognized as an important tool in the anti-tumor armamentarium. The goal of therapy is to aid the immune system in recognition and destruction of tumor cells by enhancing its ability to react to tumor antigens...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29258739/combination-immunotherapy-of-muc1-mrna-nano-vaccine-and-ctla-4-blockade-effectively-inhibits-growth-of-triple-negative-breast-cancer
#17
Lina Liu, Yuhua Wang, Lei Miao, Qi Liu, Sara Musetti, Jun Li, Leaf Huang
Triple negative breast cancer (TNBC), which constitutes 10%-20% of all breast cancers, is associated with aggressive progression, a high rate of metastasis, and poor prognosis. The treatment of patients with TNBC remains a great clinical challenge. Preclinical reports support the combination immunotherapy of cancer vaccines and immune checkpoint blockades in non-immunogenic tumors. In this study, we constructed nanoparticles (NPs) to deliver an mRNA vaccine encoding tumor antigen MUC1 to dendritic cells (DCs) in lymph nodes to activate and expand tumor-specific T cells...
December 5, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29249395/synergy-of-immune-checkpoint-blockade-with-a-novel-synthetic-consensus-dna-vaccine-targeting-tert
#18
Elizabeth K Duperret, Megan C Wise, Aspen Trautz, Daniel O Villarreal, Bernadette Ferraro, Jewell Walters, Jian Yan, Amir Khan, Emma Masteller, Laurent Humeau, David B Weiner
Immune checkpoint blockade antibodies are setting a new standard of care for cancer patients. It is therefore important to assess any new immune-based therapies in the context of immune checkpoint blockade. Here, we evaluate the impact of combining a synthetic consensus TERT DNA vaccine that has improved capacity to break tolerance with immune checkpoint inhibitors. We observed that blockade of CTLA-4 or, to a lesser extent, PD-1 synergized with TERT vaccine, generating more robust anti-tumor activity compared to checkpoint alone or vaccine alone...
November 21, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29248428/irradiation-enhances-abscopal-anti-tumor-effects-of-antigen-specific-immunotherapy-through-regulating-tumor-microenvironment
#19
Ming-Cheng Chang, Yu-Li Chen, Han-Wei Lin, Ying-Cheng Chiang, Chi-Fang Chang, Shu-Feng Hsieh, Chi-An Chen, Wei-Zen Sun, Wen-Fang Cheng
Ionizing radiation therapy is a well-established method of eradicating locally advanced tumors. Here, we examined whether local RT enhanced the potency of an antigen-specific DNA vaccine, and we investigated the possible underlying mechanism. Using the HPV16 E6/E7+ syngeneic TC-1 tumor, we evaluated the combination of CTGF/E7 vaccination with local irradiation with regard to synergistic antigen-specific immunity and anti-tumor effects. Tumor-bearing mice treated with local RT (6 Gy twice weekly) and CTGF/E7 DNA vaccination exhibited dramatically increased numbers of E7-specific CD8+ cytotoxic T cell precursors, higher titers of anti-E7 Abs, and significantly reduced tumor size...
November 21, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29245977/the-cancer-testis-antigen-sperm-protein-17-a-new-biomarker-and-immunological-target-in-head-and-neck-squamous-cell-carcinoma
#20
Christopher A Schutt, Leonardo Mirandola, Jose A Figueroa, Diane D Nguyen, Joehassin Cordero, Klauss Bumm, Benjamin L Judson, Maurizio Chiriva-Internati
Head and Neck Squamous Cell Carcinoma is a deadly and locally aggressive malignancy that frequently portends a poor prognosis. Since current treatment modalities including surgery, chemotherapy and radiation are heavily debilitating and often result in recurrence intense efforts have been put into the development of novel less toxic and more lasting treatment strategies. Recently, immunotherapy has been proposed as a promising alternative that could potentially meet these requirements. SP17 is a validated cancer-testis antigen in multiple myeloma, ovarian cancer and non-small cell lung cancer...
November 21, 2017: Oncotarget
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