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cytotoxic t cell therapy

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https://www.readbyqxmd.com/read/29344274/immunotherapy-of-patient-with-hepatocellular-carcinoma-using-cytotoxic-t-lymphocytes-ex-vivo-activated-with-tumor-antigen-pulsed-dendritic-cells
#1
Ying Wang, Xijing Yang, Yi Yu, Zenghui Xu, Yan Sun, Hui Liu, Jingbo Cheng, Min Liu, Bibo Sha, Linfang Li, Na Ding, Zhong Li, Huajun Jin, Qijun Qian
Purpose The aim of this study was to evaluate the clinical response of immunotherapy with dendritic cell-cytotoxic T lymphocytes (DC-CTLs) in patients with hepatocellular carcinoma (HCC). Method Sixty-eight patients with a confirmed diagnosis of HCC and who received follow-up until December 2015 were enrolled. We measured immune phenotypes of DCs and activated T cells using flow cytometry and clinical indexes using an electrochemiluminescence method. Results DCs exhibited up-regulation of the maturation markers CD83, CD80, CD11c, and CD86 on day8...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29341283/mogamulizumab-induced-phosensitivity-in-patients-with-mycosis-fungoides-and-other-t-cell-neoplasms
#2
Y Masuda, K Tatsuno, S Kitano, H Miyazawa, J Ishibe, M Aoshima, T Shimauchi, T Fujiyama, T Ito, Y Tokura
BACKGROUND: Mogamulizumab (Mog) is a defucosylated, therapeutic monoclonal antibody, targeting CCR4, and was first approved in Japan for the treatment of adult T cell leukaemia/lymphoma (ATLL), followed by cutaneous T cell lymphoma and peripheral T cell lymphoma. OBJECTIVE: To retrospectively investigate development of photosensitivity in patients with mycosis fungoides and other T cell neoplasms after treatment with Mog. METHODS: We treated 7 cutaneous lymphoma patients with Mog...
January 16, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29339738/dna-methyltransferase-inhibition-upregulates-mhc-i-to-potentiate-cytotoxic-t-lymphocyte-responses-in-breast-cancer
#3
Na Luo, Mellissa J Nixon, Paula I Gonzalez-Ericsson, Violeta Sanchez, Susan R Opalenik, Huili Li, Cynthia A Zahnow, Michael L Nickels, Fei Liu, Mohammed N Tantawy, Melinda E Sanders, H Charles Manning, Justin M Balko
Potentiating anti-tumor immunity by inducing tumor inflammation and T cell-mediated responses are a promising area of cancer therapy. Immunomodulatory agents that promote these effects function via a wide variety of mechanisms, including upregulation of antigen presentation pathways. Here, we show that major histocompatibility class-I (MHC-I) genes are methylated in human breast cancers, suppressing their expression. Treatment of breast cancer cell lines with a next-generation hypomethylating agent, guadecitabine, upregulates MHC-I expression in response to interferon-γ...
January 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29337259/mathematical-modeling-of-tumor-induced-immunosuppression-by-myeloid-derived-suppressor-cells-implications-for-therapeutic-targeting-strategies
#4
Seyed Peyman Shariatpanahi, Seyed Pooya Shariatpanahi, Keivan Madjidzadeh, Moustapha Hassan, Manuchehr Abedi-Valugerdi
Myeloid-derived suppressor cells (MDSCs) belong to immature myeloid cells that are generated and accumulated during the tumor development. MDSCs strongly suppress the anti-tumor immunity and provide conditions for tumor progression and metastasis. In this study, we present a mathematical model based on ordinary differential equations (ODE) to describe tumor-induced immunosuppression caused by MDSCs. The model consists of four equations and incorporates tumor cells, cytotoxic T cells (CTLs), natural killer (NK) cells and MDSCs...
January 11, 2018: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29336888/lxr-apoe-activation-restricts-innate-immune-suppression-in-cancer
#5
Masoud F Tavazoie, Ilana Pollack, Raissa Tanqueco, Benjamin N Ostendorf, Bernardo S Reis, Foster C Gonsalves, Isabel Kurth, Celia Andreu-Agullo, Mark L Derbyshire, Jessica Posada, Shugaku Takeda, Kimia N Tafreshian, Eric Rowinsky, Michael Szarek, Roger J Waltzman, Elizabeth A Mcmillan, Connie Zhao, Monica Mita, Alain Mita, Bartosz Chmielowski, Michael A Postow, Antoni Ribas, Daniel Mucida, Sohail F Tavazoie
Therapeutic harnessing of adaptive immunity via checkpoint inhibition has transformed the treatment of many cancers. Despite unprecedented long-term responses, most patients do not respond to these therapies. Immunotherapy non-responders often harbor high levels of circulating myeloid-derived suppressor cells (MDSCs)-an immunosuppressive innate cell population. Through genetic and pharmacological approaches, we uncovered a pathway governing MDSC abundance in multiple cancer types. Therapeutic liver-X nuclear receptor (LXR) agonism reduced MDSC abundance in murine models and in patients treated in a first-in-human dose escalation phase 1 trial...
January 9, 2018: Cell
https://www.readbyqxmd.com/read/29332326/carcinogenic-potential-of-antitumor-therapies-is-the-risk-predictable
#6
Ivanka Nenova, Janet Grudeva-Popova
The growing number of successfully cured cancer patients has created a new field in oncogenesis. The life expectancy of such patients has increased, however this favorable event may create enough time for epigenetic events to occur which can cause a new carcinognic event, i.e. a secondary malignancy. The terms in use are second primary malignancies as well as therapy-related neoplasms in case the treatment of the first neoplasm is a direct cause. Second primary malignancies can be hematological neoplasms or solid tumors, with solid tumors having higher frequency...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29332184/neurologic-complications-of-immune-checkpoint-inhibitors
#7
Avi Fellner, Chen Makranz, Michal Lotem, Felix Bokstein, Alisa Taliansky, Shai Rosenberg, Deborah T Blumenthal, Jacob Mandel, Suzana Fichman, Elena Kogan, Israel Steiner, Tali Siegal, Alexander Lossos, Shlomit Yust-Katz
Immune checkpoint inhibitors (ICPIs) have recently emerged as a novel treatment for cancer. These agents, transforming the field of oncology, are not devoid of toxicity and cause immune-related side effects which can involve any organ including the nervous system. In this study, we present 9 patients (7 men and 2 women) with neurologic complications secondary to ICPI treatment. These included meningoencephalitis, limbic encephalitis, polyradiculitis, cranial polyneuropathy, myasthenic syndrome and myositis...
January 13, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29329591/prospects-for-chimeric-antigen-receptor-modified-t-cell-therapy-for-solid-tumors
#8
REVIEW
Erhao Zhang, Jieyi Gu, Hanmei Xu
The potential for adoptive cell immunotherapy as a treatment against cancers has been demonstrated by the remarkable response in some patients with hematological malignancies using autologous T cells endowed with chimeric antigen receptors (CARs) specific for CD19. Clinical efficacy of CAR-T cell therapy for the treatment of solid tumors, however, is rare due to physical and biochemical factors. This review focuses on different aspects of multiple mechanisms of immunosuppression in solid tumors. We characterize the current state of CAR-modified T cell therapy and summarize the various strategies to combat the immunosuppressive microenvironment of solid tumors, with the aim of promoting T cell cytotoxicity and enhancing tumor cell eradication...
January 12, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29329556/cancer-immunotherapy-beyond-immune-checkpoint-inhibitors
#9
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/29329051/non-genetic-engineering-of-cytotoxic-t-cells-to-target-il-4-receptor-enhances-tumor-homing-and-therapeutic-efficacy-against-melanoma
#10
Gowri Rangaswamy Gunassekaran, Chae-Moon Hong, Sri Murugan Poongkavithai Vadevoo, Lianhua Chi, Padmanaban Guruprasath, Byung-Cheol Ahn, Ha-Jeong Kim, Tae Heung Kang, Byungheon Lee
Adoptive transfer of cytotoxic T lymphocytes (CTLs) has been used as an immunotherapy in melanoma. However, the tumor homing and therapeutic efficacy of transferred CTLs against melanoma remain unsatisfactory. Interleukin-4 receptor (IL-4R) is commonly up-regulated in tumors including melanoma. Here, we studied whether IL-4R-targeted CTLs exhibit enhanced tumor homing and therapeutic efficacy against melanoma. CTLs isolated from mice bearing melanomas were non-genetically engineered with IL4RPep-1, an IL-4R-binding peptide, using a membrane anchor composed of dioleylphosphatidylethanolamine...
January 8, 2018: Biomaterials
https://www.readbyqxmd.com/read/29328488/synthesis-and-application-of-131i-fulvestrant-as-a-targeted-radiation-drug-for-endocrine-therapy-in-human-breast-cancer
#11
Guobing Yin, Bin Zeng, Zhiping Peng, Ying Liu, Lu Sun, Changan Liu
The aim of this study was to label fulvestrant (an endocrine therapy drug for breast cancer) with radioiodine and to evaluate the effect of 131I-fulvestrant on inhibiting the growth of human breast cancer and its influence on major organs in nude mice. Fulvestrant was labeled with radioiodine using a modified chloramine T method, and its chemical properties were assessed using traditional methods. The binding affinity of 131I-fulvestrant was measured by radioligand binding assays, and its antiproliferative activity was determined by MTT assays...
January 11, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29328445/the-effects-of-interleukin-2-and-rad-p53-as-a-treatment-for-glioblastoma
#12
Hai-Bo Qiao, Jia Li, Lian-Jie Lv, Ben-Jin Nie, Peng Lu, Feng Xue, Zhi-Ming Zhang
Interleukin 2 (IL-2) is an anti-cancer cytokine that stimulates T cell propagation, triggering innate and adaptive immunity. IL-2 has been used for cancer therapy and has achieved curative effects. Recombinant adenovirus p53 injection (rAd‑p53) is a gene therapeutic agent that may improve the prognosis of patients with glioblastoma (GBM). In the present study, the effect of combined IL‑2 and rAd‑p53 treatment was studied. The ability of IL‑2 to stimulate immunoregulation and the ability of p53 to induce apoptosis for GBM was researched in the GBM tumor model...
January 9, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29327047/histopathological-and-inflammatory-features-of-chronically-discharging-open-mastoid-cavities-secondary-analysis-of-a-randomized-clinical-trial
#13
Darius Henatsch, Sultan Alsulami, Adriaan M Duijvestijn, Jack P Cleutjens, Carine J Peutz-Kootstra, Robert J Stokroos
Importance: Many patients with an open radical mastoid cavity experience therapy-resistant otorrhea. Little is known about the underlying histopathological substrate of unstable cavities and the correlation with treatment failure. Objective: To study the histopathological and inflammatory features of chronically discharging open radical mastoid cavities and the influence of different treatments. Design, Setting, and Participants: This secondary analysis of a randomized clinical trial was a histopathology study of tissue samples of a cohort of 30 patients with a chronically discharging open mastoid cavity...
January 11, 2018: JAMA Otolaryngology—Head & Neck Surgery
https://www.readbyqxmd.com/read/29326816/immune-checkpoint-inhibition-prospects-for-prevention-and-therapy-of-hepatocellular-carcinoma
#14
REVIEW
Caryn L Elsegood, Janina Ee Tirnitz-Parker, John K Olynyk, George Ct Yeoh
The global prevalence of liver cancer is rapidly rising, mostly as a result of the amplified incidence rates of viral hepatitis, alcohol abuse and obesity in recent decades. Treatment options for liver cancer are remarkably limited with sorafenib being the gold standard for advanced, unresectable hepatocellular carcinoma but offering extremely limited improvement of survival time. The immune system is now recognised as a key regulator of cancer development through its ability to protect against infection and chronic inflammation, which promote cancer development, and eliminate tumour cells when present...
November 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29319049/mechanisms-of-resistance-to-immune-checkpoint-inhibitors
#15
REVIEW
Russell W Jenkins, David A Barbie, Keith T Flaherty
Immune checkpoint inhibitors (ICI) targeting CTLA-4 and the PD-1/PD-L1 axis have shown unprecedented clinical activity in several types of cancer and are rapidly transforming the practice of medical oncology. Whereas cytotoxic chemotherapy and small molecule inhibitors ('targeted therapies') largely act on cancer cells directly, immune checkpoint inhibitors reinvigorate anti-tumour immune responses by disrupting co-inhibitory T-cell signalling. While resistance routinely develops in patients treated with conventional cancer therapies and targeted therapies, durable responses suggestive of long-lasting immunologic memory are commonly seen in large subsets of patients treated with ICI...
January 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29316940/gamma-delta-%C3%AE-%C3%AE-t-cells-friend-or-foe-in-cancer-development
#16
REVIEW
Yijing Zhao, Chao Niu, Jiuwei Cui
BACKGROUND: γδ T cells are a distinct subgroup of T cells containing T cell receptors (TCRs) γ and TCR δ chains with diverse structural and functional heterogeneity. As a bridge between the innate and adaptive immune systems, γδ T cells participate in various immune responses during cancer progression. Because of their direct/indirect antitumor cytotoxicity and strong cytokine production ability, the use of γδ T cells in cancer immunotherapy has received a lot of attention over the past decade...
January 10, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29316291/immunomodulation-characteristics-by-thermal-ablation-therapy-in-cancer-patients
#17
Wuwei Yang, Wei Wang, Bing Liu, Baorang Zhu, Jing Li, Debao Xu, Yanli Ni, Li Bai, Guangxian Liu
AIM: Thermal ablation therapy has recently emerged as a promising noninvasive treatment modality for localized solid malignancies. Except its direct tumor-cell-killing effect on local tumor tissues, the immunomodulatory effect has also long been noticed which too has substantial effect on clinical outcome, but it is complicated. Though much has been investigated and rich evidences have been achieved, the fundamental state and profile of immunomodulation by thermal ablation in cancer patients, its exact mechanism, especially the systematic mechanism, and its effect on antitumor immunity remain unclear...
January 8, 2018: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29312633/the-synergistic-antitumor-effect-of-arsenic-trioxide-combined-with-cytotoxic-t-cells-in-pulmonary-metastasis-model-of-colon-cancer
#18
Lei Wang, Wentao Liang, Na Peng, Xiang Hu, Yingxin Xu, Zhong Liu
Adoptive T cell therapy, including cytotoxic T lymphocytes (CTLs), represents a promising non-toxic anticancer strategy. The effects of this therapy can be impaired by tumor-infiltrated regulatory T cells (Tregs). Autologous murine CTLs acquired using cryopreservation exhibited a cytotoxic effect equivalent to that of conventional CTLs. The killing activity of CTLs was enhanced significantly using arsenic trioxide (ATO), accompanied by reduction in Tregs in vitro. Results using a pulmonary metastasis model of colon cancer indicated that compared with the control group, ATO group, and CTLs group, metastatic node number decreased significantly (p<0...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29306975/combination-of-mppa-pdt-and-hsv1-tk-gcv-gene-therapy-on-prostate-cancer
#19
Liming Liang, Wenxiang Bi, Weiwen Chen, Yani Lin, Yuanyuan Tian
We combined pyropheophorbide-a methyl ester, photodynamic therapy (MPPa-PDT), 670 ± 10 nm, 4 mW/cm2, with herpes simplex virus type 1 thymidine kinase/ganciclovir (HSV1-TK/GCV) to improve the therapeutic effect. We built HSV1-TK expression vector GV230-TK and we observed a bright green fluorescence under fluorescence microscope. It indicated the recombinant plasmid was transfected into PC-3M prostate cancer cells successfully. As the abundant glucose-regulated protein 78 (GRP78) promoter in PC-3M cells can cause active expression of HSV1-TK, cell protein was collected for western blot to determine the expression of HSV1-TK...
January 6, 2018: Lasers in Medical Science
https://www.readbyqxmd.com/read/29302251/immunotherapy-for-non-small-cell-lung-cancer-current-status-and-future-obstacles
#20
REVIEW
Ju Hwan Cho
Lung cancer is one of the leading causes of death worldwide. There are 2 major subtypes of lung cancer, non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). Studies show that NSCLC is the more prevalent type of lung cancer that accounts for approximately 80%-85% of cases. Although, various treatment methods, such as chemotherapy, surgery, and radiation therapy have been used to treat lung cancer patients, there is an emergent need to develop more effective approaches to deal with advanced stages of tumors...
December 2017: Immune Network
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