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Anti-tumor vaccines

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https://www.readbyqxmd.com/read/28628010/-the-main-stages-of-the-preparation-of-viable-tumor-cells-of-bladder-cancer-from-isolation-of-the-tumor-material-till-cryopreservation-of-cell-lines
#1
T Slavyanskaya, S -Salnikova
The development of personalized autologous dendritic cell anti-tumor vaccines (PDPW) against bladder cancer (BC) is a relevant issue that covers many aspects required for its standardization. The article presents personal experimental studies related to development of optimal conditions of transportation of biological material; temperature and temporary modes for the storage of the samples; the materials about the optimal method of disaggregation of the biomaterial; there has been shown a comparative analysis of different methods of tumor disaggregation; the selection of nutritious growth mediums and growth factors for urothelial carcinoma cells (UCC), the conditions of cryopreservation of tumor cells for maximum UCC viability, potentially suitable for creating PDPW against BC...
May 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28624783/malignant-pericytes-expressing-gt198-give-rise-to-tumor-cells-through-angiogenesis
#2
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...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28624137/effect-of-tlr-ligands-co-encapsulated-with-multiepitopic-antigen-in-nanoliposomes-targeted-to-human-dcs-via-fc-receptor-for-cancer-vaccines
#3
Felix Rueda, Christina Eich, Begoña Cordobilla, Pere Domingo, Gerardo Acosta, Fernando Albericio, Luis J Cruz, Joan C Domingo
Nanoliposomes (NLs) hold promise as new highly specific nanomedicine for anti-tumor vaccines, since they could be targeted to specific receptors on dendritic cell (DC) to induce maturation and activation and increase the anti-tumor immune response. Here we studied a NLs formulation targeted or not to FcR (the receptor for the IgG Fc fragment) for the treatment of androgen-responsive prostate cancer. Luteinizing-hormone-releasing hormone (LHRH) peptide (B- and T-cell epitopes), in tandem with a tetanus toxoid T-helper epitope (830-844 region) and several TLR (Toll-Like Receptor) ligands as adjuvants were co-encapsulated...
June 10, 2017: Immunobiology
https://www.readbyqxmd.com/read/28618135/self-assembled-nano-immunostimulant-for-synergistic-immune-activation
#4
Zhan-Yi Sun, Pu-Guang Chen, Yan-Fang Liu, Lei Shi, Bo-Dou Zhang, Jun-Jun Wu, Yu-Fen Zhao, Yong-Xiang Chen, Yan-Mei Li
Immunotherapy has become one of the most promising therapies for the treatment of diseases. Chemical molecule immunostimulants and nanomaterial immunostimulant systems are indispensable for the activation of the immune system in cancer immunotherapy. Here we report a strategy of self-assembled nano-immunostimulant (SANI) for synergistic immune activation. Three immunostimulants self-assembled into nanoparticles through electrostatic interactions. SANI showed strong synergistic immunostimulation in macrophages...
June 15, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28617554/the-study-on-specific-umbilical-blood-dc-vaccine-for-beige-nude-mice-loaded-human-colorectal-carcinoma-to-induce-anti-tumor-immunity
#5
Z-X Fu, J-S Han, F Liu, Z-L Zhao, D-B Li, L Shi, J-T Dong, Y Zhou, J-H Cai
OBJECTIVE: This study is to observe the immunosuppression of CD137L transfected umbilical blood Dcs (Dendritic cell) vaccine to tumor development of SCID/ Beige nude mice. MATERIALS AND METHODS: Samples of umbilical blood in the childbirth pregnant women were collected by density gradient centrifugation. Umbilical cord blood dendritic cells (Dcs) were transfected by specific CD137L via LipofectamineTM method and cells were harvested. Meanwhile, the peripheral blood of volunteers was collected to isolate Dcs, the Dcs were cultured for 5 days and hatched with SW-1116 cells antigen...
May 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28615225/enhanced-therapeutic-efficacy-and-memory-of-tumor-specific-cd8-t-cells-by-ex-vivo-pi3k-%C3%AE-inhibition
#6
Rasha Abu-Eid, Shamim Ahmad, Yuan Lin, Mason Webb, Zuzana Berrong, Rajeev K Shrimali, Takumi Kumai, Sudha Ananth, Paulo C Rodriguez, Esteban Celis, John E Janik, Mikayel Mkrtichyan, Samir N Khleif
Inhibition of specific Akt isoforms in CD8+ T cells promotes favored differentiation into memory versus effector cells, the former of which are superior in mediating anti-tumor immunity. In this study, we investigated the role of upstream PI3K isoforms in CD8+ T cell differentiation and assessed the potential use of PI3K isoform-specific inhibitors to favorably condition CD8+ T cells for adoptive cell therapy. The phenotype and proliferative ability of tumor antigen specific CD8+ T cells was assessed in the presence of PI3K-α, -β, or -δ inhibitors...
June 14, 2017: Cancer Research
https://www.readbyqxmd.com/read/28612942/cytomegalovirus-vector-expressing-rae-1%C3%AE-induces-enhanced-anti-tumor-capacity-of-murine-cd8-t-cells
#7
Tihana Tršan, Kristina Vuković, Petra Filipović, Ana Lesac Brizić, Niels A W Lemmermann, Kilian Schober, Dirk H Busch, William J Britt, Martin Messerle, Astrid Krmpotić, Stipan Jonjić
Designing CD8(+) T-cell vaccines, which would provide protection against tumors is still considered a great challenge in immunotherapy. Here we show the robust potential of cytomegalovirus (CMV) vector expressing the NKG2D ligand RAE-1γ as CD8(+) T cell-based vaccine against malignant tumors. Immunization with the CMV vector expressing RAE-1γ, delayed tumor growth or even provided complete protection against tumor challenge in both prophylactic and therapeutic settings. Moreover, a potent tumor control in mice vaccinated with this vector can be further enhanced by blocking the immune checkpoints TIGIT and PD-1...
June 14, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28608115/phase-i-trial-of-antigen-targeted-autologous-dendritic-cell-based-vaccine-with-in-vivo-activation-of-inducible-cd40-for-advanced-prostate-cancer
#8
Guru Sonpavde, John D McMannis, Yu Bai, Mamatha R Seethammagari, Joan M C Bull, Victoria Hawkins, Theresa K Dancsak, Natasha Lapteva, Jonathan M Levitt, Annemarie Moseley, David M Spencer, Kevin M Slawin
This phase I trial reports the safety and activity of BPX101, a second-generation antigen-targeted autologous antigen presenting cell (APC) vaccine in men with metastatic castration-resistant prostate cancer (mCRPC). To manufacture BPX101, APCs collected in a single leukapheresis were transduced with adenoviral vector Ad5f35 encoding inducible human (ih)-CD40, followed by incubation with protein PA001, which contains the extracellular domain of human prostate-specific membrane antigen. The ih-CD40 represents a modified chimeric version of the dendritic cell (DC) co-stimulatory molecule, CD40, which responds to a bioinert membrane-permeable activating dimerizer drug, rimiducid (AP1903), permitting temporally controlled, lymphoid-localized, DC-specific activation...
June 12, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28607601/evaluation-of-attenuated-tumor-antigens-and-the-implications-for-peptide-based-cancer-vaccine-development
#9
J S Berry, T J Vreeland, D F Hale, D O Jackson, A F Trappey, J M Greene, M O Hardin, G S Herbert, G T Clifton, G E Peoples
INTRODUCTION: Peptide vaccines offer anti-tumor efficacy with very low toxicity. However, repeat stimulation with an immunogenic peptide leads to activation induced cell death (AICD), decreasing efficacy. We engineered variants of an immunogenic peptide (E39) and tested their ability to induce a robust, sustainable immune response. METHODS: Multiple variants of E39 were created by exchanging 1 or 2 amino acids. We tested the PBMC proliferation, cytokine production and cytolytic activity induced by each variant peptide...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28607581/pembrolizumab-in-cervical-cancer-latest-evidence-and-clinical-usefulness
#10
REVIEW
Edith Borcoman, Christophe Le Tourneau
Cervical cancer is the fourth most common cause of cancer-related deaths in women worldwide. With the development of detection of precancerous lesions and preventive human papillomavirus (HPV) vaccination program, a survival improvement has been observed in these patients in developed countries, although disparities in accessibility to treatments exist across countries. While early-stage cervical cancer can be curable with surgery, prognosis of patients who recur remains poor, with limited treatment options...
June 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28604556/immunologic-response-elicited-in-breast-cancer-patients-receiving-a-neugcgm3-based-vaccine-as-adjuvant-therapy
#11
Anet Valdes-Zayas, Zuyen Gonzalez, Vladimir Mulens, Aliz M Vega, Kirenia Perez, Patricia Lorenzo-Luaces, Maria C Rubio, Anabely Estevez, Idelmis Curbelo, Luis E Fernandez, Tania Crombet, Zaima Mazorra
This study aimed to investigate the immunogenicity of a cancer vaccine consisting of the NeuGcGM3 ganglioside combined with the outer membrane protein complex of Neisseria meningitides to form very small size particles. The vaccine is administered together with Montanide ISA51, as adjuvant treatment for breast cancer patients. After surgical resection and standard first-line chemo/radiotherapy, breast cancer patients in stage II-III were enrolled in a phase III clinical trial and allocated into 2 strata, according to the number of positive lymph nodes [stratum I (0-3); stratum II (≥4)]...
June 9, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28601925/enhanced-stimulation-of-human-tumor-specific-t-cells-by-dendritic-cells-matured-in-the-presence-of-interferon-%C3%AE-and-multiple-toll-like-receptor-agonists
#12
Tanja Lövgren, Dhifaf Sarhan, Iva Truxová, Bhavesh Choudhary, Roeltje Maas, Jeroen Melief, Maria Nyström, Ulrika Edbäck, Renee Vermeij, Gina Scurti, Michael Nishimura, Giuseppe Masucci, Alex Karlsson-Parra, Andreas Lundqvist, Lars Adamson, Rolf Kiessling
Dendritic cell (DC) vaccines have been demonstrated to elicit immunological responses in numerous cancer immunotherapy trials. However, long-lasting clinical effects are infrequent. We therefore sought to establish a protocol to generate DC with greater immunostimulatory capacity. Immature DC were generated from healthy donor monocytes by culturing in the presence of IL-4 and GM-CSF and were further differentiated into mature DC by the addition of cocktails containing different cytokines and toll-like receptor (TLR) agonists...
June 10, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28601924/tgf-%C3%AE-1-silenced-leukemia-cell-derived-exosomes-target-dendritic-cells-to-induce-potent-anti-leukemic-immunity-in-a-mouse-model
#13
Fang Huang, Jiangbo Wan, Siguo Hao, Xiaohui Deng, Linjun Chen, Liyuan Ma
Tumor-derived exosomes (TEX) can induce a specific antitumor immune response and have been developed as a promising tumor vaccine. Despite promising preclinical data, TEX exhibit relatively low efficacy and limited clinical benefit in clinical trials. In the present study, we investigated whether exosomes from the TGF-β1 silenced L1210 cells (LEXTGF-β1si) can enhance the efficacy of DC-based vaccines. We silenced TGF-β1 in L1210 cells with a lentiviral shRNA vector and prepared the LEXTGF-β1si. It was shown that LEXTGF-β1si can significantly decrease TGF-β1 expression of dendritic cells (DC) and effectively promote their maturation and immune function...
June 10, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28586072/treatment-of-colon-cancer-cells-with-5-fluorouracil-can-improve-the-effectiveness-of-rna-transfected-antitumor-dendritic-cell-vaccine
#14
Carolina V De Almeida, Jofer A Zamame, Graziela G Romagnoli, Cecilia P Rodrigues, Marianna B Magalhães, Amedeo Amedei, Ramon Kaneno
Non-cytotoxic concentrations of selected chemotherapeutic agents amplify the antigen presentation capacity of dendritic cells (DCs) and are able to increase the immunogenicity of the colon cancer cell lineage HCT‑116, as previously demonstrated by our group. Since this functional alteration was associated with changes in gene expression, we aimed to evaluate whether transcriptional changes of tumor cells can be transferred to DCs, increasing their ability to induce a specific antitumor response. Therefore, HCT‑116 cells were treated with two different concentrations of 5-fluorouracil (5-FU), and their total RNA was transfected into human monocyte-derived DC, which function was evaluated through their ability to stimulate the proliferation of normal allogeneic T lymphocytes (MLR), and to generate cytolytic T cells...
June 1, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28583430/the-egfr-variant-iii-mutant-as-a-target-for-immunotherapy-of-glioblastoma-multiforme
#15
REVIEW
Dimitry A Chistiakov, Ivan V Chekhonin, Vladimir P Chekhonin
In epithelial tumors, the epidermal growth factor receptor (EGFR) controls key signaling pathways responsible for growth, proliferation, migration, and survival of tumor cells. The epidermal growth factor receptor variant III (EGFRvIII) is the most common EGFR mutation that occurs in up to 30% of high-grade gliomas especially glioblastoma multiforme (GBM). EGFRvIII arises from the deletion of exon 2-7 that leads to the formation of the constitutively activated mutant receptor incapable of binding any known ligand...
June 2, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28578522/evaluation-of-the-oncolytic-potential-of-r2b-mukteshwar-vaccine-strain-of-newcastle-disease-virus-ndv-in-a-colon-cancer-cell-line-sw-620
#16
Kishan K Sharma, Irsadullakhan H Kalyani, Jogeswar Mohapatra, Satish D Patel, Dharmesh R Patel, Priti D Vihol, Abhijit Chatterjee, Dinesh R Patel, Bhavesh Vyas
Virotherapy is emerging as an alternative treatment of cancer. Among the candidate oncolytic viruses (OVs), Newcastle disease virus (NDV) has emerged as a promising non-engineered OV. In the present communication, we explored the oncolytic potential of R2B Mukteshwar strain of NDV using SW-620 colon cancer cells. SW-620 cells were xenografted in nude mice and after evaluation of the safety profile, 1 x 10(7) plaque forming units (PFU) of NDV were inoculated as virotherapeutic agent via the intratumoral (I/T) and intravenous (I/V) route...
June 3, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28571582/the-150-most-important-questions-in-cancer-research-and-clinical-oncology-series-questions-31-39-edited-by-chinese-journal-of-cancer
#17
EDITORIAL
(no author information available yet)
To accelerate our endeavors to overcome cancer, Chinese Journal of Cancer has launched a program of publishing 150 most important questions in cancer research and clinical oncology. In this article, 9 more questions are presented as follows. Question 31: How does aging process inhibit the formation of sarcoma? Question 32: Is intratumoral morphological heterogeneity the consequence of tumor genomic instability or the cause of aggressive tumor behavior? Can we identify more aggressive tumors by computationally analyzing the morphological heterogeneity of the tumor tissues? Question 33: How to pre-surgically differentiate irradiation-induced ulceration from cancerous ulceration? Question 34: Why is epidermal growth factor receptor (EGFR) 19 Del-positive tumor more sensitive to targeted therapy than EGFR 21 L858R-positive tumor in patients with non-small cell lung cancer? Question 35: Can an Epstein-Barr virus vaccine be developed to reduce the incidence of EBV-related malignancies? Question 36: What is the unique feature in sarcoma vasculature that causes the intrinsic resistance of sarcoma against anti-angiogenic therapy? Question 37: How many ways can sarcoma cells protect themselves from the attacks of cytotoxic drugs? Question 38: How stable does the tumor heterogeneity remain along with cytotoxic chemotherapy? Question 39: How to generate a prognostic classifier for diffuse low-grade gliomas by integrating genetic and epigenetic signatures with histological features?...
June 2, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/28566332/oncolytic-adenovirus-and-tumor-targeting-immune-modulatory-therapy-improve-autologous-cancer-vaccination
#18
Hong Jiang, Yisel Rivera-Molina, Karen Clise-Dwyer, Laura Bover, Luis Vence, Ying Yuan, Frederick F Lang, Carlo Toniatti, Mohammad B Hossain, Candelaria Gomez-Manzano, Juan Fueyo
Oncolytic viruses selectively lyse tumor cells, disrupt immunosuppression within the tumor and reactivate anti-tumor immunity, but they have yet to live up to their therapeutic potential. Immune checkpoint modulation has been efficacious in a variety of cancer with an immunogenic microenvironment, but is associated with toxicity due to nonspecific T-cell activation. Therefore, combining these two strategies would likely result in both effective and specific cancer therapy. To test the hypothesis, we first constructed oncolytic adenovirus Delta-24-RGDOX expressing the immune co-stimulator OX40 ligand (OX40L)...
May 31, 2017: Cancer Research
https://www.readbyqxmd.com/read/28565847/recombinant-bacille-calmette-gu%C3%A3-rin-coexpressing-ag85b-ifn-%C3%AE-enhances-the-cell-mediated-immunity-in-c57bl-6-mice
#19
Wei Liu, Ying Xu, Hongbo Shen, Jingran Yan, Enzhuo Yang, Honghai Wang
The only available vaccine against pulmonary tuberculosis is Bacille Calmette-Guérin (BCG). As the efficacy reported of the vaccine is not up to the mark, there is an urgent need to develop improved anti-tuberculosis vaccines. Antigen 85B (Ag85B) is a very promising vaccine candidate molecule of Mycobacterium tuberculosis and interferon (IFN)-γ and has been considered the most attractive correlate of protective immunity. The aim of this study was to construct a novel recombinant BCG (rBCG) to secrete Ag85B and mouse IFN-γ under control of the Mycobacterial heat shock protein 60 (hsp60) promoter and the antigen signal sequence...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28564605/a-tlr3-specific-adjuvant-relieves-innate-resistance-to-pd-l1-blockade-without-cytokine-toxicity-in-tumor-vaccine-immunotherapy
#20
Yohei Takeda, Keisuke Kataoka, Junya Yamagishi, Seishi Ogawa, Tsukasa Seya, Misako Matsumoto
Cancer patients having anti-programmed cell death-1 (PD-1)/PD ligand 1 (L1)-unresponsive tumors may benefit from advanced immunotherapy. Double-stranded RNA triggers dendritic cell (DC) maturation to cross-prime antigen-specific cytotoxic T lymphocytes (CTLs) via Toll-like receptor 3 (TLR3). The TLR3-specific RNA agonist, ARNAX, can induce anti-tumor CTLs without systemic cytokine/interferon (IFN) production. Here, we have developed a safe vaccine adjuvant for cancer that effectively implements anti-PD-L1 therapy...
May 30, 2017: Cell Reports
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