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https://www.readbyqxmd.com/read/29791768/vaccine-immunotherapy-with-arnax-induces-tumor-specific-memory-t-cells-and-durable-anti-tumor-immunity-in-mouse-models
#1
Yohei Takeda, Sumito Yoshida, Ken Takashima, Noriko Ishii-Mugikura, Hiroaki Shime, Tsukasa Seya, Misako Matsumoto
Immunological checkpoint blockade therapies benefit a limited population of cancer patients. We have previously shown that vaccine immunotherapy with TLR3-adjuvant and tumor antigen overcomes anti-programmed death ligand-1 (PD-L1) resistance in mouse tumor models. In this study, four different OVA-expressing tumor cell lines were implanted into syngeneic mice and subjected to antitumor immunotherapy using ARNAX and whole OVA protein. ARNAX is a Toll-like receptor 3-specific agonist that does not activate the MAVS pathway, and thus does not induce systemic inflammation...
May 23, 2018: Cancer Science
https://www.readbyqxmd.com/read/29782928/a-mathematical-approach-to-effects-of-ctls-on-cancer-virotherapy-in-the-second-injection-of-virus
#2
A Ashyani, O RabieiMotlagh, H M Mohammadinezhad
This paper proposes a planar delay differential equation for cancer virotherapy. The model simulates the situation in which an oncolytic virus is injected for the second time, and the immune system suppresses the viral infection with a time delay. Our purpose is to provide theoretical conditions so that the therapy can be continued successfully. With the help of the characteristic equation, we examine the singularities and their local stability. Hopf bifurcation is also investigated around the endemic singularity...
May 18, 2018: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29773224/early-env-specific-ctls-effectively-suppress-viral-replication-in-shiv-controller-macaques
#3
Jin Fan, Hua Liang, Tao Shen, Shuo Wang, Xiaolin Ji, Cassian Yee, Fengmin Lu, Yiming Shao
Early immunological events in acute HIV infection are thought to fundamentally influence long-term disease outcomes. Though the contribution of Gag-specific CD8 T cell responses to early viral control is well established, little is known about the role of Env-specific CD8 T cell responses in controlling viral replication during acute infection. In a macaque simian-human immunodeficiency virus (SHIV) model, some macaques who were able to control SHIV replication after ART interruption showed expansion of Env-specific CD8 T cell responses during acute infection, compared to macaques who progressed to viral rebound...
May 5, 2018: Cellular Immunology
https://www.readbyqxmd.com/read/29772373/a-novel-c-type-lectin-from-the-sea-cucumber-apostichopus-japonicus-ajctl-2-with-preferential-binding-of-d-galactose
#4
Hui Wang, Zhuang Xue, Zhaoqun Liu, Weilin Wang, Feifei Wang, Ying Wang, Lingling Wang, Linsheng Song
C-type lectins (CTLs) are Ca2+ dependent carbohydrate-binding proteins that share structural homology in their carbohydrate-recognition domains (CRDs). In the present study, a novel CTL was identified from sea cucumber Apostichopus japonicus (named as AjCTL-2). The deduced amino acid sequence of AjCTL-2 was homologous to CTLs from other animals with the identities ranging from 33% to 40%. It contained a canonical signal peptide at the N-terminus, a low density lipoprotein receptor class A (LDLa), a C1r/C1s/Uegf/bone morphogenetic protein 1 (CUB), and a CRD with two motif Glu-Pro-Asn (EPN) and Trp-Asn-Asp (WND) in Ca2+ binding site 2...
May 14, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29768177/expression-of-the-dna-binding-factor-tox-promotes-the-encephalitogenic-potential-of-microbe-induced-autoreactive-cd8-t-cells
#5
Nicolas Page, Bogna Klimek, Mathias De Roo, Karin Steinbach, Hadrien Soldati, Sylvain Lemeille, Ingrid Wagner, Mario Kreutzfeldt, Giovanni Di Liberto, Ilena Vincenti, Thomas Lingner, Gabriela Salinas, Wolfgang Brück, Mikael Simons, Rabih Murr, Jonathan Kaye, Dietmar Zehn, Daniel D Pinschewer, Doron Merkler
Infections are thought to trigger CD8+ cytotoxic T lymphocyte (CTL) responses during autoimmunity. However, the transcriptional programs governing the tissue-destructive potential of CTLs remain poorly defined. In a model of central nervous system (CNS) inflammation, we found that infection with lymphocytic choriomeningitis virus (LCMV), but not Listeria monocytogenes (Lm), drove autoimmunity. The DNA-binding factor TOX was induced in CTLs during LCMV infection and was essential for their encephalitogenic properties, and its expression was inhibited by interleukin-12 during Lm infection...
May 15, 2018: Immunity
https://www.readbyqxmd.com/read/29752021/hyperthermic-treatment-at-56-%C3%A2-c-induces-tumour-specific-immune-protection-in-a-mouse-model-of-prostate-cancer-in-both-prophylactic-and-therapeutic-immunization-regimens
#6
Francesco De Sanctis, Sara Sandri, Matteo Martini, Marta Mazzocco, Alessandra Fiore, Rosalinda Trovato, Stefano Garetto, Davide Brusa, Stefano Ugel, Silvia Sartoris
Most active cancer immunotherapies able to induce a long-lasting protection against tumours are based on the activation of tumour-specific cytotoxic T lymphocytes (CTLs). Cell death by hyperthermia induces apoptosis followed by secondary necrosis, with the production of factors named "danger associated molecular pattern" (DAMP) molecules (DAMPs), that activate dendritic cells (DCs) to perform antigen uptake, processing and presentation, followed by CTLs cross priming. In many published studies, hyperthermia treatment of tumour cells is performed at 42-45 °C; these temperatures mainly promote cell surface expression of DAMPs...
May 8, 2018: Vaccine
https://www.readbyqxmd.com/read/29748898/cystatin-f-as-a-regulator-of-immune-cell-cytotoxicity
#7
REVIEW
Janko Kos, Milica Perišić Nanut, Mateja Prunk, Jerica Sabotič, Esmeralda Dautović, Anahid Jewett
Cysteine cathepsins are lysosomal peptidases involved in the regulation of innate and adaptive immune responses. Among the diverse processes, regulation of granule-dependent cytotoxicity of cytotoxic T-lymphocytes (CTLs) and natural killer (NK) cells during cancer progression has recently gained significant attention. The function of cysteine cathepsins is regulated by endogenous cysteine protease inhibitors-cystatins. Whereas other cystatins are generally cytosolic or extracellular proteins, cystatin F is present in endosomes and lysosomes and is thus able to regulate the activity of its target directly...
May 10, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29744934/modelling-how-reversal-of-immune-exhaustion-elicits-cure-of-chronic-hepatitis-c-after-the-end-of-treatment-with-direct-acting-antiviral-agents
#8
Subhasish Baral, Rahul Roy, Narendra M Dixit
A fraction of chronic hepatitis C patients treated with direct-acting antivirals (DAAs) achieved sustained virological responses (SVR), or cure, despite having detectable viremia at the end of treatment (EOT). This observation, termed EOT+ /SVR, remains puzzling and precludes rational optimization of treatment durations. One hypothesis to explain EOT+ /SVR, the immunologic hypothesis, argues that the viral decline induced by DAAs during treatment reverses the exhaustion of cytotoxic T lymphocytes (CTLs), which then clear the infection after treatment...
May 9, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29740425/induction-of-type-i-interferons-by-therapeutic-nanoparticle-based-vaccination-is-indispensable-to-reinforce-cytotoxic-cd8-t-cell-responses-during-chronic-retroviral-infection
#9
Torben Knuschke, Olga Rotan, Wibke Bayer, Sebastian Kollenda, Julia Dickow, Kathrin Sutter, Wiebke Hansen, Ulf Dittmer, Karl S Lang, Matthias Epple, Jan Buer, Astrid M Westendorf
T cell dysfunction and immunosuppression are characteristic for chronic viral infections and contribute to viral persistence. Overcoming these burdens is the goal of new therapeutic strategies to cure chronic infectious diseases. We recently described that therapeutic vaccination of chronic retrovirus infected mice with a calcium phosphate (CaP) nanoparticle (NP)-based vaccine carrier, functionalized with CpG and viral peptides is able to efficiently reactivate the CD8+ T cell response and improve the eradication of virus infected cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29739434/gastric-cancer-vaccines-synthesized-using-a-tlr7-agonist-and-their-synergistic-antitumor-effects-with-5-fluorouracil
#10
Xiaodong Wang, Yu Liu, Yuwen Diao, Ningning Gao, Yanyan Wan, Jingjing Zhong, Huali Zheng, Zhulin Wang, Guangyi Jin
BACKGROUND: Vaccines play increasingly important roles in cancer treatment due to their advantages of effective targeting and few side effects. Our laboratory has attempted to construct vaccines by conjugating TLR7 agonists with tumor-associated antigens. Furthermore, immunochemotherapy has recently become an appealing approach to cancer therapy. 5-fluorouracil (5-FU), a commonly used chemotherapeutic agent, can reportedly potently and selectively kill tumor-associated MDSCs in vivo. METHODS: Gastric cancer vaccines were synthesized by the covalent attachment of our TLR7 agonist with the gastric cancer antigen MG7-Ag tetra-epitope, leading to T7 - ML (linear tetra-epitope) and T7 - MB (branched tetra-epitope)...
May 8, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29727573/nanocrystalline-titanium-metal-organic-frameworks-for-highly-efficient-and-flexible-perovskite-solar-cells
#11
UnJin Ryu, Seohyeon Jee, Joon-Suh Park, Il Ki Han, Ju Ho Lee, Minwoo Park, Kyung Min Choi
Flexible perovskite solar cells (PSCs) have attracted considerable attention due to their excellent performance, low-cost, and great potential as an energy supplier for soft electronic devices. In particular, the design of charge transporting layers (CTLs) is crucial to the development of highly efficient and flexible PSCs. Herein, nanocrystalline Ti-based metal-organic framework (nTi-MOF) particles are synthesized to have ca. 6 nm in diameter. These are then well-dispersed in alcohol solvents in order to generate electron transporting layers (ETLs) in PSCs under ambient temperatures using a spin coating process...
May 4, 2018: ACS Nano
https://www.readbyqxmd.com/read/29721531/extra-large-pore-mesoporous-silica-nanoparticles-enabling-co-delivery-of-high-amounts-of-protein-antigen-and-toll-like-receptor-9-agonist-for-enhanced-cancer-vaccine-efficacy
#12
Bong Geun Cha, Ji Hoon Jeong, Jaeyun Kim
Cancer vaccine aims to invoke antitumor adaptive immune responses to detect and eliminate tumors. However, the current dendritic cells (DCs)-based cancer vaccines have several limitations that are mostly derived from the ex vivo culture of patient DCs. To circumvent the limitations, direct activation and maturation of host DCs using antigen-carrying materials, without the need for isolation of DCs from patients, are required. In this study, we demonstrate the synthesis of extra-large pore mesoporous silica nanoparticles (XL-MSNs) and their use as a prophylactic cancer vaccine through the delivery of cancer antigen and danger signal to host DCs in the draining lymph nodes...
April 25, 2018: ACS Central Science
https://www.readbyqxmd.com/read/29718486/identification-and-characterization-of-c-type-lectins-in-ostrinia-furnacalis-lepidoptera-pyralidae
#13
Dongxu Shen, Lei Wang, Jiayue Ji, Qizhi Liu, Chunju An
C-type lectins (CTLs) are a large family of calcium-dependent carbohydrate-binding proteins. They function primarily in cell adhesion and immunity by recognizing various glycoconjugates. We identified 14 transcripts encoding proteins with one or two CTL domains from the transcriptome from Asian corn borer, Ostrinia furnacalis (Guenée; Lepidoptera: Pyralidae). Among them, five (OfCTL-S1 through S5) only contain one CTL domain, the remaining nine (OfIML-1 through 9) have two tandem CTL domains. Five CTL-Ss and six OfIMLs have a signal peptide are likely extracellular while another two OfIMLs might be cytoplasmic...
March 1, 2018: Journal of Insect Science
https://www.readbyqxmd.com/read/29710479/antigen-adjuvant-effects-of-icariin-in-enhancing-tumor-specific-immunity-in-mastocytoma-bearing-dba-2j-mice
#14
Xiaodi Zhang, Zhichen Kang, Qingjie Li, Jin Zhang, Sha Cheng, Hao Chang, Shanshan Wang, Shufang Cao, Tie Li, Jiawei Li, Yishan Wang, Yu Song, Hao Yu
Cancer immunotherapy has attracted much attention in recent years because of the ability of immune system to identify tumor cells and limit their growth. Icariin (ICA) is a natural flavonoid glucoside isolated from Epimedium plants and has shown a variety of pharmacological activities such as anti-inflammatory effects, immunological regulation and anticancer potency. Furthermore, it has immunoadjuvant effects on enhancing Th1-immune response, suggesting that ICA may serve as an adjuvant for cancer immunotherapy...
March 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29706956/embryonic-fibroblasts-promote-antitumor-cytotoxic-effects-of-cd8-t-cells
#15
Yingyu Qin, Jung Hoon Shin, Jeong-Ho Yoon, Se-Ho Park
Adoptive CD8+ T cell therapy has emerged as an important modality for the treatment of cancers. However, the significant drawback of transfused T cells is their poor survival and functionality in response to tumors. To overcome this limitation, an important consideration is exploring a culture condition to generate superior antitumor cytotoxic T lymphocytes (CTLs) for adoptive therapy. Here, we provide a novel approach to generate potent CTL clones in mouse embryonic fibroblast-conditioned medium (MEF-CM). We found CTLs derived with MEF-CM have higher potential in long-term persistence in tumor bearing and non-tumor-bearing mice...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29705247/transfer-of-gene-corrected-t-cells-corrects-humoral-and-cytotoxic-defects-in-x-linked-lymphoproliferative-disease-xlp1
#16
Neelam Panchal, Ben Houghton, Begona Diez, Sujal Ghosh, Ida Ricciardelli, Adrian J Thrasher, H Bobby Gaspar, Claire Booth
BACKGROUND: XLP1 arises from mutations in the SH2D1A gene encoding SAP, an adaptor protein expressed in T, NK and NKT cells. Defects lead to abnormalities of T and NK cell cytotoxicity and T cell dependent humoral function. Clinical manifestations include haemophagocytic lymphohistiocytosis (HLH), lymphoma and dysgammaglobulinaemia. Curative treatment is limited to haematopoietic stem cell transplant with outcome reliant on a good donor match. OBJECTIVES: As most symptoms arise from defective T cell function, we investigated whether transfer of SAP gene corrected T cells could reconstitute known effector cell defects...
April 26, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29702123/first-characterization-of-two-c-type-lectins-of-the-tubeworm-alaysia-sp-from-a-deep-sea-hydrothermal-vent
#17
Qian-Wen Jin, Qing-Lei Sun, Jian Zhang, Li Sun
C-type lectins (CTLs) play an important role in innate immune defense. In this study, we identified and characterized two CTLs (Lec1 and Lec2) from the tubeworm Alaysia sp. collected from a hydrothermal vent in Pacmanus. Lec1 and Lec2 possess the typical CTL domain but share low sequence identities (10.8%-20.4%) with known CTLs. Recombinant (r) of Lec1 and Lec2 bound to various PAMPs and a wide arrange of bacteria from neritic and deep-sea environments in a Ca2+ -independent manner, but only rLec1 caused agglutination of the bound bacteria...
April 24, 2018: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29700809/the-opposing-roles-of-cd4-t-cells-in-anti-tumor-immunity
#18
REVIEW
Tomasz Ahrends, Jannie Borst
Cancer immunotherapy focuses mainly on anti-tumor activity of CD8+ cytotoxic T lymphocytes (CTLs). CTLs can directly kill all tumor cell types, provided that they carry recognizable antigens. However, CD4+ T cells also play important roles in anti-tumor immunity. CD4+ T cells can either suppress or promote anti-tumor CTL response, both in secondary lymphoid organs or in the tumor. In this review, we highlight opposing mechanisms of conventional (Tconv) and regulatory (Treg) T cells at both sites. We outline how current cancer immunotherapy strategies affect both subsets and how selective modulation of each subset is important to maximize the clinical response of cancer patients...
April 27, 2018: Immunology
https://www.readbyqxmd.com/read/29699516/reduction-of-mhc-i-expression-limits-t-lymphocyte-mediated-killing-of-cancer-initiating-cells
#19
Brian J Morrison, Jason C Steel, John C Morris
BACKGROUND: It has been proposed that cancer establishment, maintenance, and recurrence may be attributed to a unique population of tumor cells termed cancer-initiating cells (CICs) that may include characteristics of putative cancer stem cell-like cells. Studies in lung cancer have shown that such cells can be enriched and propagated in vitro by culturing tumor cells in serum-free suspension as tumorspheres. CICs have been characterized for their phenotype, stem cell-like qualities, and their role in establishing tumor and maintaining tumor growth...
April 26, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29696308/role-of-mda5-and-interferon-i-in-dendritic-cells-for-t-cell-expansion-by-anti-tumor-peptide-vaccines-in-mice
#20
Hussein Sultan, Juan Wu, Takumi Kumai, Andres M Salazar, Esteban Celis
Cytotoxic T lymphocytes (CTLs) are effective components of the immune system capable of destroying tumor cells. Generation of CTLs using peptide vaccines is a practical approach to treat cancer. We have previously described a peptide vaccination strategy that generates vast numbers of endogenous tumor-reactive CTLs after two sequential immunizations (prime-boost) using poly-ICLC adjuvant, which stimulates endosomal toll-like receptor 3 (TLR3) and cytoplasmic melanoma differentiation antigen 5 (MDA5). Dendritic cells (DCs) play an important role not only in antigen presentation but are critical in generating costimulatory cytokines that promote CTL expansion...
April 25, 2018: Cancer Immunology, Immunotherapy: CII
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