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cytotoxic t cell therapy

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https://www.readbyqxmd.com/read/28530155/an-oncolytic-adenovirus-encoding-decorin-and-gm-csf-inhibits-tumor-growth-in-a-colorectal-tumor-model-by-targeting-pro-tumorigenic-signals-and-via-immune-activation
#1
Zhao Liu, Yuefeng Yang, Xiaoyan Zhang, Hao Wang, Weidong Xu, Hua Wang, FengJun Xiao, Zhigang Bai, Hongwei Yao, Xuemei Ma, Lan Jin, Chu-Tse Wu, Prem Seth, Zhongtao Zhang, Lisheng Wang
In advanced and metastatic stages of colorectal cancer (CRC), reduced sensitivity to conventional strategies is still a major obstacle to successful treatments. Decorin is an important regulator in the development and progression of various cancers. To examine if CRC patients have altered decorin levels, expression of decorin and its target genes, Met and vascular endothelial growth factor A (VEGFA) were analyzed in their tumors. Compared to normal tissues, decorin expression was reduced in CRC patients' tumors, while, there were increased Met and VEGFA levels...
May 20, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28528668/trpv1-channels-in-immune-cells-and-hematological-malignancies
#2
Sofia A Omari, Murray J Adams, Dominic P Geraghty
Transient receptor potential vanilloid-1 (TRPV1) is a member of the TRP family of channels that are responsible for nociceptive, thermal, and mechanical sensations. Originally associated exclusively with sensory neurons, TRPV1 is now known to be present in almost all organs, including cells of the immune system, where TRPV1 has been shown to play a pivotal role in inflammation and immunity. Monocytes, macrophages, and dendritic cells express TRPV1, with both mouse and human studies suggesting that TRPV1 activation protects against endotoxin-induced inflammation...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28528510/immunogenomics-using-genomics-to-personalize-cancer-immunotherapy
#3
Rance C Siniard, Shuko Harada
While the use of genomic data has the potential to revolutionize patient care, there is still much work to be done with regard to the transformation of host-tumor interactions into favorable clinical outcomes for our patients. High-throughput technologies, such as next-generation sequencing (NGS), have rapidly advanced our understanding of oncology, and we are learning that most tumors do not simply possess consistently mutated genes that are responsible for tumorigenesis, facilitating the need for personalized cancer therapy...
May 20, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28521478/enhancement-of-antitumor-immunity-by-combination-of-anti-ctla-4-antibody-and-radioimmunotherapy-through-the-suppression-of-tregs
#4
Cheol-Hun Son, Jaeho Bae, Hong-Rae Lee, Kwangmo Yang, You-Soo Park
Cytotoxic T lymphocyte antigen-4 (CTLA-4) is expressed during cluster of differentiation (CD)4+ T-cell activation and terminates immune responses by interrupting CD28-enhanced activation. In addition, CTLA-4 is known to be constitutively expressed in regulatory T-cells (Tregs) and to contribute to immune suppression by enhancing the suppressive function of Tregs. However, the molecular mechanisms underlying CTLA-4-mediated Treg suppression remains incompletely understood. Furthermore, it is uncertain whether the in vivo immune suppressive functions of CTLA-4 are mediated only by a reduction in the level of conventional T-cell activity, or enhancement of Treg function...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28515346/the-novel-complex-combination-of-alum-cpg-odn-and-hh2-as-adjuvant-in-cancer-vaccine-effectively-suppresses-tumor-growth-in-vivo
#5
Yaomei Tian, Meng Li, Chaoheng Yu, Rui Zhang, Xueyan Zhang, Rong Huang, Lian Lu, Fengjiao Yuan, Yingzi Fan, Bailing Zhou, Ke Men, Heng Xu, Li Yang
Single-component adjuvant is prone to eliciting a specific type of Th1 or Th2 response. So, the development of combinatorial adjuvants inducing a robust mixed Th1/Th2 response is a promising vaccination strategy against cancer. Here, we describe a novel combination of aluminum salts (alum), CpG oligodeoxynucleotide (CpG) and innate defense regulator peptide HH2 for improving anti-tumor immune responses. The CpG-HH2 complex significantly enhanced the production of IFN-γ, TNF-α and IL-1β, promoted the uptake of antigen and strengthened the activation of p38, Erk1/2 and NF-κB in vitro, compared to CpG or HH2 alone...
April 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28512265/chaetocin-enhances-dendritic-cell-function-via-the-induction-of-heat-shock-protein-and-cancer-testis-antigens-in-myeloma-cells
#6
Manh-Cuong Vo, Thanh-Nhan Nguyen-Pham, Hyun-Ju Lee, Sung-Hoon Jung, Nu-Ri Choi, My-Dung Hoang, Hyeoung-Joon Kim, Je-Jung Lee
Dendritic cells (DC)-based vaccines are considered useful in cancer immuno-therapy, and the interactions of DC and dying tumor cells are important and promising for cancer immunotherapy. We investigated whether chaetocin could be used to induce death of myeloma cells, for loading onto DCs can affect DCs function. In this study, we show that the dying myeloma cells treated with chaetocin resulted in the induction of heat shock protein (HSP) 90, which was inhibited by antioxidant N-acetyl cysteine, and showed an increase in the expression of MAGE-A3 and MAGE-C1/CT7...
April 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28512174/dynamic-changes-in-pd-l1-expression-and-immune-infiltrates-early-during-treatment-predict-response-to-pd-1-blockade-in-melanoma
#7
Ricardo E Vilain, Alexander M Menzies, James S Wilmott, Hojabr Kakavand, Jason Madore, Alexander Guminski, Elizabeth Liniker, Ben Kong, Adam Cooper, Julie R Howle, Robyn P M Saw, Valerie Jakrot, Serigne Lo, John F Thompson, Matteo S Carlino, Richard F Kefford, Georgina V Long, Richard A Scolyer
Disruption of PD-L1/cytotoxic T-cell PD-1 signalling by immune-checkpoint inhibitors improves survival in cancer patients. This study sought to identify changes in tumoral PD-L1 expression and tumor-associated immune cell flux with anti-PD1 therapies in melanoma patients, particularly early during treatment, and correlate them with treatment response<br /><br />Experimental Design: Forty-six tumor biopsies from 23 unresectable AJCC Stage III/IV melanoma patients receiving pembrolizumab/nivolumab were analyzed...
May 16, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28510446/modularly-constructed-synthetic-granzyme-b-molecule-enables-interrogation-of-intracellular-proteases-for-targeted-cytotoxicity
#8
Patrick Ho, Christopher Ede, Yvonne Y Chen
Targeted therapies promise to increase the safety and efficacy of treatments against diseases ranging from cancer to viral infections. However, the vast majority of targeted therapeutics relies on the recognition of extracellular biomarkers, which are rarely restricted to diseased cells and are thus prone to severe and sometimes-fatal off-target toxicities. In contrast, intracellular antigens present a diverse yet underutilized repertoire of disease markers. Here, we report a protein-based therapeutic platform-termed Cytoplasmic Oncoprotein VErifier and Response Trigger (COVERT)-which enables the interrogation of intracellular proteases to trigger targeted cytotoxicity...
May 22, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28508448/a-novel-multi-epitope-vaccine-from-mmsa-1-and-dkk1-for-multiple-myeloma-immunotherapy
#9
Chenyang Lu, Shan Meng, Yanxia Jin, Wanggang Zhang, Zongfang Li, Fang Wang, Feng Wang-Johanning, Yongchang Wei, Hailing Liu, Honglei Tu, Dan Su, Aili He, Xingmei Cao, Fuling Zhou
The identification of novel tumour-associated antigens is urgently needed to improve the efficacy of immunotherapy for multiple myeloma (MM). In this study, we identified a membrane protein MMSA-1 (multiple myeloma special antigen-1) that was specifically expressed in MM and exhibited significantly positive correlation with MM. We then identified HLA-A*0201-restricted MMSA-1 epitopes and tested their cytotoxic T lymphocyte (CTL) response. The MMSA-1 epitope SLSLLTIYV vaccine was shown to induce an obvious CTL response in vitro...
May 16, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28507809/t-cell-therapy-targeting-a-public-neoantigen-in-microsatellite-instable-colon-cancer-reduces-in-vivo-tumor-growth
#10
Else M Inderberg, Sébastien Wälchli, Marit R Myhre, Sissel Trachsel, Hilde Almåsbak, Gunnar Kvalheim, Gustav Gaudernack
T-cell receptor (TCR) transfer is an attractive strategy to increase the number of cancer-specific T cells in adoptive cell therapy. However, recent clinical and pre-clinical findings indicate that careful consideration of the target antigen is required to limit the risk of off-target toxicity. Directing T cells against mutated proteins such as frequently occurring frameshift mutations may thus be a safer alternative to tumor-associated self-antigens. Furthermore, such frameshift mutations result in novel polypeptides allowing selection of TCRs from the non-tolerant T-cell repertoire circumventing the problem of low affinity TCRs due to central tolerance...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28506444/monocyte-lineage-derived-il-6-does-not-affect-chimeric-antigen-receptor-t-cell-function
#11
Nathan Singh, Ted J Hofmann, Zachary Gershenson, Bruce L Levine, Stephan A Grupp, David T Teachey, David M Barrett
BACKGROUND AIMS: Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has demonstrated remarkable success in targeting B-cell malignancies but is often complicated by serious systemic toxicity in the form of cytokine release syndrome (CRS). CRS symptoms are primarily mediated by interleukin 6 (IL-6), and clinical management has focused on inhibition of IL-6 signaling. The cellular source and function of IL-6 in CRS remain unknown. METHODS: Using co-culture assays and data from patients on our clinical CAR T-cell trials, we investigated the cellular source of IL-6, as well as other CRS-associated cytokines, during CAR T-cell activation...
May 11, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28505536/design-synthesis-molecular-docking-and-cytotoxic-evaluation-of-novel-2-furybenzimidazoles-as-vegfr-2-inhibitors
#12
Mona A Abdullaziz, Heba T Abdel-Mohsen, Ahmed M El Kerdawy, Fatma A F Ragab, Mamdouh M Ali, Sherifa M Abu-Bakr, Adel S Girgis, Hoda I El Diwani
Inhibition of angiogenesis through inhibition of vascular endothelial growth factor receptor 2 (VEGFR-2) has been applied in cancer therapy because of its important role in promoting cancer growth and metastasis. In the presented study, a series of benzimidazol-furan hybrids was designed and synthesized through facile synthetic pathways. Evaluation of the synthesized compounds for their in vitro cytotoxic activity against breast (MCF-7) and hepatocellular (HepG2) carcinoma cell lines was performed. Two of the synthesized conjugates, 10b and 15, showed potent antiproliferative properties against MCF-7 cell line (IC50 = 21...
April 26, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28505480/triphenyltin-iv-benzoates-with-diazenyl-imino-scaffold-exhibiting-remarkable-apoptosis-mediated-by-reactive-oxygen-species
#13
Tushar S Basu Baul, Dhrubajyoti Dutta, Andrew Duthie, Ritika Prasad, Nishant Kumar Rana, Biplob Koch, Edward R T Tiekink
The cytotoxic potency of a series of triphenyltin(IV) compounds of general composition [Ph3Sn(L(n))] (1-6) has been probed in vitro employing MDA-MB-231 (human breast cancer) and HeLa (human cervical cancer) cell lines, where L(n)=L(1-3); isomeric 2/3/4-{(E)-2-[4-(dimethylamino)phenyl]diazenyl}benzoates and L(4-6) are their corresponding isoelectronic imino analogues 2/3/4-[(E)-{[4-(dimethylamino)phenyl]methylidene}amino]benzoates. Compounds 1-6 have been characterized by elemental analysis and their spectroscopic properties were studied using IR and NMR ((1)H, (13)C, (119)Sn) techniques...
April 29, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28505010/tackling-immunomonitoring-in-gastrointestinal-cancer
#14
Maëlle Anciaux, Caroline Vandeputte, Alain Hendlisz
PURPOSE OF REVIEW: The growing awareness that the immune system is a key player in the antitumoral response and the excellent clinical results achieved in some settings with anti-programmed cell death 1 (PD1)/programmed death ligand 1 (PDL1) and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) drugs has led to the rise of immunotherapy as a supplement or an alternative to conventional cancer treatment. The high costs associated with these therapies, their significant toxicity and the need to understand and circumvent immune escape mechanisms raise the urgent need for immunological assessment of therapy response...
May 12, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28499235/probiotics-a-non-conventional-therapy-for-oral-lichen-planus
#15
REVIEW
Xiao Han, Jing Zhang, Yaqin Tan, Gang Zhou
Oral lichen planus (OLP) is a common T-cell mediated chronic inflammatory disease. Although the etiology is still unclear, present studies suggest that the composition of the oral microbiota and psychological problems are implicated in the etiology of OLP. The pathogenesis of OLP includes mainly antigen-specific and non-specific mechanisms. Antigen-specific mechanisms involve T-cell activation following antigen presentation and apoptosis of basal keratinocytes triggered by CD8(+) cytotoxic T cells, while non-specific mechanisms consist of matrix metalloproteinase over-expression and mast cell degranulation in OLP lesions...
April 26, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28498953/pathological-role-of-anti-cd4-antibodies-in-hiv-infected-immunologic-non-responders-under-viral-suppressive-antiretroviral-therapy
#16
Zhenwu Luo, Zhen Li, Lisa Martin, Zhuang Wan, Eric G Meissner, Enrique Espinosa, Hao Wu, Xiaocong Yu, Pingfu Fu, Maria Anna Julia Westerink, J Michael Kilby, Jennifer Wu, Lei Huang, Sonya L Heath, Zihai Li, Wei Jiang
Increased mortality and morbidity occurs in human immunodeficiency virus (HIV)-infected patients who fail to increase CD4+ T cell counts despite achieving viral suppression with antiretroviral therapy (ART). Here we identified an underlying mechanism. Significantly elevated plasma levels of anti-CD4 IgGs were found in HIV+ immunologic non-responders (CD4+ T cell counts ≤ 350 cells/μl) compared to HIV+ immunologic responders (CD4+ T cell counts ≥ 500 cells/μl) and healthy controls. Higher plasma level of anti-CD4 IgG correlated with blunted CD4+ T cell recovery...
May 11, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28498618/phase-i-clinical-trial-of-cell-division-associated-1-cdca1-peptide-vaccination-for-castration-resistant-prostate-cancer
#17
Wataru Obara, Fuminori Sato, Kazuyoshi Takeda, Renpei Kato, Yoichiro Kato, Mitsugu Kanehira, Ryo Takata, Hiromitsu Mimata, Tamotsu Sugai, Yusuke Nakamura, Tomoaki Fujioka
We screened cell division associated 1 (CDCA1) as an oncogene that is overexpressed on several cancers, including prostate cancer. We also identified a highly immunogenic HLA-A*2402-restricted epitope peptide corresponding to part of the CDCA1 protein. We conducted a phase I clinical trial for patients with castration resistant prostate cancer (CRPC) using a CDCA1 peptide vaccination. Twelve patients having HLA-A*2402 with CRPC after failure of docetaxel chemotherapy were enrolled. They received subcutaneous administration of the CDCA1 peptide as an emulsion with Montanide ISA51VG once a week in a dose-escalation manner (doses of 1...
May 12, 2017: Cancer Science
https://www.readbyqxmd.com/read/28498033/development-and-characterization-of-novel-monoclonal-antibodies-against-human-dnam-1
#18
Genki Okumura, Fumie Abe, Rei Hirochika, Akira Shibuya, Kazuko Shibuya
DNAM-1 (CD226) is an activating immunoreceptor expressed on lymphocytes and myeloid cells. CD155 and CD112 are the ligands for DNAM-1. DNAM-1 plays an important role in tumor immunity mediated by CD8(+) T cells and NK cells. Moreover, the interaction of DNAM-1 with the ligands contributed to the development of acute graft versus host disease (GVHD) and treatment with anti-DNAM-1 monoclonal antibodies (mAb) dramatically improved acute GVHD in a mouse model, suggesting that DNAM-1 may be a good molecular target for therapy to acute GVHD in human...
May 12, 2017: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/28497863/ctla-4-expressed-by-foxp3-treg-cells-prevents-inflammatory-tissue-attack-and-not-t-cell-priming-in-arthritis
#19
Katrin Klocke, Rikard Holmdahl, Kajsa Wing
Cytotoxic T-lymphocyte antigen 4 (CTLA-4)-mediated regulation of already tolerized autoreactive T cells is critical for understanding autoimmune responses. While defects in CTLA-4 contribute to abnormal FOXP3(+) regulatory T cell (Treg) function in rheumatoid arthritis (RA) its role in autoreactive T cells remains elusive. We studied immunity towards the dominant collagen type-II (CII) T cell epitope in collagen-induced arthritis (CIA) both in the heterologous setting and in the autologous setting where CII is mutated at position E266D in mouse cartilage...
May 12, 2017: Immunology
https://www.readbyqxmd.com/read/28497777/phase-i-ii-clinical-trial-to-assess-safety-and-efficacy-of-intratumoral-and-subcutaneous-injection-of-hvj-e-in-castration-resistant-prostate-cancer-patients
#20
K Fujita, Y Nakai, A Kawashima, T Ujike, A Nagahara, T Nakajima, T Inoue, C M Lee, M Uemura, Y Miyagawa, Y Kaneda, N Nonomura
Inactivated Sendai virus particles (hemagglutinating virus of Japan envelope (HVJ-E)) have a novel antitumor effect: HVJ-E fused to prostate cancer cells via cell surface receptor causes apoptosis of prostate cancer cells in vitro and in vivo. HVJ-E also induces antitumor immunity by activating natural killer (NK) cells and cytotoxic T cells and suppressing regulatory T cells in vivo. We conducted an open-label, single-arm, phase I/II clinical trial in patients with castration-resistant prostate cancer (CRPC) to determine the safety and efficacy of intratumoral and subcutaneous injection of HVJ-E...
May 12, 2017: Cancer Gene Therapy
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