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https://www.readbyqxmd.com/read/29147614/exploiting-a-new-strategy-to-induce-immunogenic-cell-death-to-improve-dendritic-cell-based-vaccines-for-lymphoma-immunotherapy
#1
B Montico, C Lapenta, M Ravo, D Martorelli, E Muraro, B Zeng, E Comaro, M Spada, S Donati, S M Santini, R Tarallo, G Giurato, F Rizzo, A Weisz, F Belardelli, R Dolcetti, J Dal Col
Although promising, the clinical benefit provided by dendritic cell (DC)-based vaccines is still limited and the choice of the optimal antigen formulation is still an unresolved issue. We have developed a new DC-based vaccination protocol for aggressive and/or refractory lymphomas which combines the unique features of interferon-conditioned DC (IFN-DC) with highly immunogenic tumor cell lysates (TCL) obtained from lymphoma cells undergoing immunogenic cell death. We show that treatment of mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL) cell lines with 9-cis-retinoic acid and IFNα (RA/IFNα) induces early membrane exposure of Calreticulin, HSP70 and 90 together with CD47 down-regulation and enhanced HMGB1 secretion...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29146244/extending-antigen-release-from-particulate-vaccines-results-in-enhanced-antitumor-immune-response
#2
Chintan H Kapadia, Shaomin Tian, Jillian L Perry, David Sailer, J Christopher Luft, Joseph M DeSimone
Tumor-specific CD8(+) cytotoxic T lymphocytes (CTLs) play a critical role in an anti-tumor immune response. However, vaccination intended to elicit a potent CD8(+) T cell responses employing tumor-associated peptide antigens, are typically ineffective due to poor immunogenicity. Previously, we engineered a polyethylene glycol (PEG) hydrogel-based subunit vaccine for the delivery of an antigenic peptide and CpG (adjuvant) to elicit potent CTLs. In this study, we further examined the effect of antigen release kinetics on their induced immune responses...
November 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29145974/immunotherapy-for-triple-negative-breast-cancer-existing-challenges-and-exciting-prospects
#3
Hongyan Jia, Cristina I Truica, Bin Wang, Yanhong Wang, Xingcong Ren, Harold A Harvey, Jianxun Song, Jin-Ming Yang
Patients with breast tumors that do not express the estrogen receptor, the progesterone receptor, nor Her-2/neu are hence termed "triple negatives", and generally have a poor prognosis, with high rates of systemic recurrence and refractoriness to conventional therapy regardless of the choice of adjuvant treatment. Thus, more effective therapeutic options are sorely needed for triple-negative breast cancer (TNBC), which occurs in approximately 20% of diagnosed breast cancers. In recent years, exploiting intrinsic mechanisms of the host immune system to eradicate cancer cells has achieved impressive success, and the advances in immunotherapy have yielded potential new therapeutic strategies for the treatment of this devastating subtype of breast cancer...
May 2017: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/29137359/granulysin-expressed-in-a-humanized-mouse-model-induces-apoptotic-cell-death-and-suppresses-tumorigenicity
#4
Ya-Wen Hsiao, Tsung-Ching Lai, Yu-Hsiang Lin, Chia-Yi Su, Jih-Jong Lee, Albert Taiching Liao, Yuan-Feng Lin, Shu-Chen Hsieh, Alexander T H Wu, Michael Hsiao
Granulysin (GNLY) is a cytolytic and proinflammatory protein expressed in activated human cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Conventional mouse models cannot adequately address the triggering mechanism and immunopathological pathways in GNLY-associated diseases due to lack of the GNLY gene in the mouse genome. Therefore, we generated a humanized immune system (HIS) mouse model by transplanting human umbilical cord blood mononuclear cells into NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl) /SzJ (NSG) mice after sublethally irradiation...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29135580/wake-me-up-before-you-go-a-strategy-to-reduce-the-latent-hiv-reservoir
#5
Nicolas Chomont, Afam A Okoye, David Favre, Lydie Trautmann
: In the quest to eliminate or reduce the HIV reservoir, shock and kill strategies require the combined administration of a latency reversing agent (LRA) to reactivate the latent reservoir and an intervention to boost effector functions to clear this reservoir. Both parts of this strategy are quite inefficient when LRAs are administered to HIV-infected individuals on suppressive ART for several years, possibly due to low levels of induced antigen expression, negative impact of LRAs on clearance mechanisms, and very low number of effective cytotoxic T cells (CTLs)...
November 10, 2017: AIDS
https://www.readbyqxmd.com/read/29126798/cd4-t-cell-help-confers-a-cytotoxic-t-cell-effector-program-including-coinhibitory-receptor-downregulation-and-increased-tissue-invasiveness
#6
Tomasz Ahrends, Aldo Spanjaard, Bas Pilzecker, Nikolina Bąbała, Astrid Bovens, Yanling Xiao, Heinz Jacobs, Jannie Borst
CD4(+) T cells optimize the cytotoxic T cell (CTL) response in magnitude and quality, by unknown molecular mechanisms. We here present the transcriptomic changes in CTLs resulting from CD4(+) T cell help after anti-cancer vaccination or virus infection. The gene expression signatures revealed that CD4(+) T cell help during priming optimized CTLs in expression of cytotoxic effector molecules and many other functions that ensured efficacy of CTLs throughout their life cycle. Key features included downregulation of PD-1 and other coinhibitory receptors that impede CTL activity, and increased motility and migration capacities...
November 6, 2017: Immunity
https://www.readbyqxmd.com/read/29123959/immunological-efficacy-of-glypican-3-peptide-vaccine-in-patients-with-advanced-hepatocellular-carcinoma
#7
Nobuhiro Tsuchiya, Toshiaki Yoshikawa, Norihiro Fujinami, Keigo Saito, Shoichi Mizuno, Yu Sawada, Itaru Endo, Tetsuya Nakatsura
We have previously conducted a phase I trial to test the efficacy of a glypican-3 (GPC3) peptide vaccine in patients with advanced hepatocellular carcinoma (HCC); however, its immunological mechanism of action remains unclear. Here, we report a pilot study conducted to evaluate the immunological mechanisms of action of this GPC3 peptide vaccine (UMIN-CTR number 000005093). Eleven patients with advanced HCC were vaccinated with the GPC3 peptide in this trial. The primary end point was GPC3 peptide-specific immune response induced by the GPC3 peptide vaccination...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29119057/dendritic-cells-based-immunotherapy
#8
REVIEW
Na Shang, Matteo Figini, Junjie Shangguan, Bin Wang, Chong Sun, Liang Pan, Quanhong Ma, Zhuoli Zhang
Dendritic cells (DCs) are the most potent antigen-presenting cells, and tumor antigen-loaded DCs (DC-vaccines) can activate tumor-specific cytotoxic T lymphocytes (CTLs) in lymphatic tissues. DC vaccination is a newly emerging and potent form of cancer immunotherapy and has clinically relevant mechanisms of action with great potential for the systemic treatment of cancers. However, clinical trials have demonstrated relatively poor therapeutic efficacy. The efficacy of DC-vaccines is strongly influenced by various techniques for the priming antigen loading onto DCs and their ability to migrate to the draining lymph nodes (LNs)...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29114389/adoptive-cell-therapy-with-cd4-t-helper-1-cells-and-cd8-cytotoxic-t-cells-enhances-complete-rejection-of-an-established-tumour-leading-to-generation-of-endogenous-memory-responses-to-non-targeted-tumour-epitopes
#9
Kunyu Li, Braeden Donaldson, Vivienne Young, Vernon Ward, Christopher Jackson, Margaret Baird, Sarah Young
The results of adoptive T-cell therapies (ACTs) are very encouraging and show clinical evidence that ACT can provide a cure for patients with metastatic disease. However, various response rates and long-term cancer remission have been observed in different ACT trials. The types of T cells, prior treatment with chemotherapy and co-administration of other immune-target therapies have been found to influence the efficacy of ACT. In this study, we investigate the ability of ACT using CD4(+) T helper 1 (Th1) cells and CD8(+) cytotoxic T lymphocytes (CTLs) to reject the growth of established B16-ovalbumin (OVA) melanoma...
October 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29112115/immunoenhancement-effects-of-glycosaminoglycan-from-apostichopus-japonicus-in-vitro-and-in-cyclophosphamide-induced-immunosuppressed-mice-studies
#10
Han Wang, Shuang Yang, Yuanhong Wang, Tingfu Jiang, Shuai Li, Zhihua Lv
In this study, the immunomodulatory activities of Apostichopus japonicus glycosaminoglycan (AHG) on the nature killer (NK) cells, cytotoxic T lymphocytes (CTLs) and cyclophosphamide (CY)-treated mice were investigated. After stimulation with multiple concentrations of AHG (0-100 μg/mL), NK cells and CTLs displayed outperformance against YAC-1 and B16 cells, respectively. Furthermore, the mitogen-induced splenic lymphocyte proliferation in CY-induced immunosuppressed mice was significantly promoted by AHG. In addition, the administration of AHG dramatically increased the splenocytes Ca(2+) concentration and the delayed-type hypersensitivity (DTH) reaction in a dose-dependent manner...
November 7, 2017: Marine Drugs
https://www.readbyqxmd.com/read/29109122/the-type-1-diabetes-resistance-locus-idd22-controls-trafficking-of-autoreactive-ctls-into-the-pancreatic-islets-of-nod-mice
#11
Robert L Whitener, Lisa Gallo Knight, Jianwei Li, Sarah Knapp, Shuyao Zhang, Mani Annamalai, Vadim M Pliner, Dongtao Fu, Ilian Radichev, Christina Amatya, Alexei Savinov, Arif Yurdagul, Shuai Yuan, John Glawe, Christopher G Kevil, Jing Chen, Scott E Stimpson, Clayton E Mathews
Type 1 diabetes (T1D) has a strong genetic component. The insulin dependent diabetes (Idd)22 locus was identified in crosses of T1D-susceptible NOD mice with the strongly T1D-resistant ALR strain. The NODcALR-(D8Mit293-D8Mit137)/Mx (NOD-Idd22) recombinant congenic mouse strain was generated in which NOD mice carry the full Idd22 confidence interval. NOD-Idd22 mice exhibit almost complete protection from spontaneous T1D and a significant reduction in insulitis. Our goal was to unravel the mode of Idd22-based protection using in vivo and in vitro models...
November 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29107688/identification-of-antigenic-peptides-from-novel-renal-cancer-stem-like-cell-antigen-dnajb8
#12
Satoshi Nishizawa, Yoshihiko Hirohashi, Hiroki Kusumoto, Takahito Wakamiya, Takashi Iguchi, Shimpei Yamashita, Akinori Iba, Kazuro Kikkawa, Yasuo Kohjimoto, Toshihiko Torigoe, Isao Hara
OBJECTIVES: To identify antigenic peptides of cancer stem-like cells (CSCs) antigen, DNAJB8, and establish a mouse CSCs-targeting immunotherapy model. MATERIALS AND METHODS: To induce DNAJB8-specific immune reaction, we stimulated human CD8(+) lymphocytes with antigen-presenting cells pulsed with a cocktail of three candidate HLA-A*24:02 restricted peptides and assessed peptide specific human cytotoxic T lymphocytes (CTLs) induction. One of the antigenic peptides showed identical amino acid sequence as corresponding mouse DNAJB8...
October 28, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29103682/expression-of-immunoproteasome-subunits-in-the-porcine-lung-alterations-during-normal-and-inflammatory-conditions
#13
Qiang Liu, Yong-Li Zhang, Shou-Ping Hu, Ze-Lin Ma, Su-Li Gao, Bin Sun, Fei Xiao, Zhuo Zhang, Xue-Hui Cai, Xi-Jun He
The elimination of infected cells by cytotoxic T lymphocytes (CTLs) occurs through interactions between T cell receptors (TCRs) and pathogen-derived antigenic peptide-major histocompatibility complex (MHC) class I complexes. The immunoproteasome (i-proteasome), which is a large proteolytic machine derived from the constitutive proteasome, is highly efficient at processing antigens for presentation on MHC class I molecules to activate CD8(+) T lymphocytes; this in turn facilitates antiviral adaptive immune responses...
October 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/29100036/nafamostat-mesilate-a-serine-protease-inhibitor-suppresses-interferon-gamma-induced-up-regulation-of-programmed-cell-death-ligand-1-in-human-cancer-cells
#14
Sadamu Homma, Kazumi Hayashi, Kosaku Yoshida, Yukiko Sagawa, Yuko Kamata, Masaki Ito
Programmed cell death ligand-1 (PD-L1) plays a pivotal role in the suppression of antitumour immunity by binding to programmed cell death-1 (PD-1) on tumouricidal cytotoxic T lymphocytes (CTLs), rendering them inactive. As blockade of PD-1/PD-L1 interaction by the monoclonal antibodies induced effective T cell-mediated antitumour response, suppression of PD-L1 expression in tumour cells by the chemical agent might contribute to treatment against malignant tumours. Nafamostat mesilate (NM), a serine protease inhibitor that is frequently used in the clinic, potently suppressed interferon-gamma (IFN-gamma)-induced up-regulation of PD-L1 in cultured human lung cancer cells (HLC-1) at both the messenger RNA (mRNA) and protein levels...
October 28, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29093272/t-cells-presenting-viral-antigens-or-autoantigens-induce-cytotoxic-t-cell-anergy
#15
Nathalie E Blachère, Dana E Orange, Emily C Gantman, Bianca D Santomasso, Graeme C Couture, Teresa Ramirez-Montagut, John Fak, Kevin J O'Donovan, Zhong Ru, Salina Parveen, Mayu O Frank, Michael J Moore, Robert B Darnell
In the course of modeling the naturally occurring tumor immunity seen in patients with paraneoplastic cerebellar degeneration (PCD), we discovered an unexpectedly high threshold for breaking CD8+ cytotoxic T cell (CTL) tolerance to the PCD autoantigen, CDR2. While CDR2 expression was previously found to be strictly restricted to immune-privileged cells (cerebellum, testes, and tumors), unexpectedly we have found that T cells also express CDR2. This expression underlies inhibition of CTL activation; CTLs that respond to epithelial cells expressing CDR2 fail to respond to T cells expressing CDR2...
November 2, 2017: JCI Insight
https://www.readbyqxmd.com/read/29079801/development-of-a-curative-therapeutic-vaccine-theravac-for-the-treatment-of-large-established-tumors
#16
Yingjie Nie, De Yang, Anna Trivett, Zhen Han, Haiyun Xin, Xin Chen, Joost J Oppenheim
Harnessing immune system to treat cancer requires simultaneous generation of tumor-specific CTLs and curtailment of tumor immunosuppressive environment. Here, we developed an immunotherapeutic regimen capable of eliminating large established mouse tumors using HMGN1, a DC-activating TLR4 agonist capable of inducing anti-tumor immunity. Intratumoral delivery of HMGN1 with low dose of Cytoxan cured mice bearing small (∅ ≈ 0.5 cm), but not large (∅ ≈ 1.0 cm) CT26 tumors. Screening for activators capable of synergizing with HMGN1 in activating DC identified R848...
October 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29070683/stability-and-expression-levels-of-hla-c-on-the-cell-membrane-modulate-hiv-1-infectivity
#17
Francesca Parolini, Priscilla Biswas, Michela Serena, Francesca Sironi, Valentina Muraro, Elisabetta Guizzardi, Lucia Cazzoletti, Maria Teresa Scupoli, Davide Gibellini, Elisabetta Ugolotti, Roberto Biassoni, Alberto Beretta, Mauro Malnati, Maria Grazia Romanelli, Donato Zipeto
HLA-C expression is associated with a differential ability to control HIV-1 infection. Higher HLA-C levels may lead to a better control of HIV-1 infection through both a higher efficiency of antigen presentation to cytotoxic T lymphocytes (CTLs), as well as the triggering of activating Killer Immunoglobulin like receptors (KIR) on NK-cells, whereas lower levels may provide a poor HIV-1 control and a rapid progression toward AIDS.We characterized the relative amount of HLA-C heterotrimers (heavy chain/β2m/peptide) and HLA-C free heavy chains on PBMC from healthy blood donors harboring both alleles with stable or unstable binding to β2m/peptide...
October 25, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29061300/mthsp70-clic1-pulsed-dendritic-cells-enhance-the-immune-response-against-ovarian-cancer
#18
Wentao Yu, Hong Qu, Guangming Cao, Chongdong Liu, Haiteng Deng, Zhenyu Zhang
Approximately 80% of ovarian cancer (OC) is diagnosed at late stages, and most patients die within 5 years of diagnosis due to recurrence or drug resistance. Novel treatments are required to improve patient survival. Immune therapy against cancer is promising; however, therapeutic vaccination has been limited by the inability of tumor antigens to induce effective immune responses. Chloride intracellular channel 1 (CLIC1) was previously identified as a possible tumor marker for OC. In this study, we constructed a recombinant protein by conjugating the extracellular domain of CLIC1 to the carboxyl terminus of Mycobacterium tuberculosis heat shock protein 70 (MtHsp70)...
December 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29061065/improving-the-potency-of-dna-vaccine-encoding-hiv-1-nef-antigen-using-two-endogenous-adjuvants-in-mouse-model
#19
B S Jafarzade, S M Sadat, R Yaghobi, A Bolhassani
BACKGROUND: DNA immunization can induce long-term immune responses, which are required to design an effective HIV vaccine. It was shown that antigen-expressing plasmids can increase the protective immunity against infectious diseases such as: influenza and malaria. However, DNA-based immunizations have poor immunogenicity, thus the use of potent immunoadjuvants can enhance their potency. METHODS: In the current study, preparation of the recombinant HIV-1 Nef, Gp96 and HMGB1 DNA constructs was performed in bacterial system...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/29059634/the-prognostic-benefit-of-tumour-infiltrating-natural-killer-cells-in-endometrial-cancer-is-dependent-on-concurrent-overexpression-of-human-leucocyte-antigen-e-in-the-tumour-microenvironment
#20
M A C Versluis, S Marchal, A Plat, G H de Bock, T van Hall, M de Bruyn, H Hollema, H W Nijman
BACKGROUND: Human Leucocyte Antigen- E (HLA-E) has been reported as both a positive and negative prognostic marker in cancer. This apparent discrepancy may be due to opposing actions of HLA-E on tumour-infiltrating immune cells. Therefore, we evaluated HLA-E expression and survival in relation to the presence of intratumoural natural killer (NK) cells and cytotoxic T cells (CTLs). METHODS: Tissue microarrays (TMAs) of endometrial tumours were used for immunohistochemical staining of parameters of interest...
October 20, 2017: European Journal of Cancer
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