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cytotoxic t cell therapy

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https://www.readbyqxmd.com/read/28921946/biomimetic-magnetosomes-as-versatile-artificial-antigen-presenting-cells-to-potentiate-t-cell-based-anticancer-therapy
#1
Qianmei Zhang, Wei Wei, Peiling Wang, Liping Zuo, Feng Li, Jin Xu, Xiaobo Xi, Xiaoyong Gao, Guanghui Ma, Hai-Yan Xie
Adoptive T-cell transfer for cancer therapy relies on both effective ex vivo T cell expansion and in vivo targeting performance. One promising but challenging method for accomplishing this purpose is to construct multifunctional artificial antigen-presenting cells (aAPCs). We herein developed biomimetic magnetosomes as versatile aAPCs, wherein magnetic nanoclusters were coated with azide-engineered leucocyte membranes and then decorated with T-cell stimuli through copper-free click chemistry. These novel nano aAPCs not only exhibited high performance for antigen-specific cytotoxic T cell (CTL) expansion and stimulation but also visually and effectively guided reinfused CTLs to tumor tissues through magnetic resonance imaging and magnetic control...
September 18, 2017: ACS Nano
https://www.readbyqxmd.com/read/28918459/hla-class-i-expression-predicts-prognosis-and-therapeutic-benefits-from-tyrosine-kinase-inhibitors-in-metastatic-renal-cell-carcinoma-patients
#2
Jiajun Wang, Li Liu, Yang Qu, Wei Xi, Yu Xia, Qi Bai, Ying Xiong, Qilai Long, Jiejie Xu, Jianming Guo
PURPOSE: Classical HLA class I antigen is highly involved in antigen presentation and adaptive immune response against tumor. In this study, we explored its predictive value for treatment response and survival in metastatic renal-cell carcinoma (mRCC) patients. EXPERIMENTAL DESIGN: A TKI cohort of 111 mRCC patients treated with sunitinib or sorafenib and a non-TKI cohort of 160 mRCC patients treated with interleukin-2 or interferon-α-based immunotherapy at a single institution were retrospectively enrolled...
September 16, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28916655/tethering-il2-to-its-receptor-il2r%C3%AE-enhances-anti-tumor-activity-and-expansion-of-natural-killer-nk92-cells
#3
Youssef Jounaidi, Joseph F Cotten, Keith W Miller, Stuart A Forman
Interleukin-2 (IL2) is an immunostimulatory cytokine for key immune cells including T cells and natural killer (NK) cells. Systemic IL2 supplementation could enhance NK-mediated immunity in a variety of diseases ranging from neoplasms to viral infection. However, its systemic use is restricted by its serious side effects and limited efficacy due to activation of T regulatory cells (Tregs). IL2 signaling is mediated through interactions with a multi-subunit receptor complex containing IL2Rα, IL2Rβ and IL2Rγ...
September 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28915659/data-driven-analysis-of-immune-infiltrate-in-a-large-cohort-of-breast-cancer-and-its-association-with-disease-progression-er-activity-and-genomic-complexity
#4
Ruth Dannenfelser, Marianne Nome, Andliena Tahiri, Josie Ursini-Siegel, Hans Kristian Moen Vollan, Vilde D Haakensen, Åslaug Helland, Bjørn Naume, Carlos Caldas, Anne-Lise Børresen-Dale, Vessela N Kristensen, Olga G Troyanskaya
The tumor microenvironment is now widely recognized for its role in tumor progression, treatment response, and clinical outcome. The intratumoral immunological landscape, in particular, has been shown to exert both pro-tumorigenic and anti-tumorigenic effects. Identifying immunologically active or silent tumors may be an important indication for administration of therapy, and detecting early infiltration patterns may uncover factors that contribute to early risk. Thus far, direct detailed studies of the cell composition of tumor infiltration have been limited; with some studies giving approximate quantifications using immunohistochemistry and other small studies obtaining detailed measurements by isolating cells from excised tumors and sorting them using flow cytometry...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915085/pooled-analysis-safety-profile-of-nivolumab-and-ipilimumab-combination-therapy-in-patients-with-advanced-melanoma
#5
Mario Sznol, Pier Francesco Ferrucci, David Hogg, Michael B Atkins, Pascal Wolter, Massimo Guidoboni, Celeste Lebbé, John M Kirkwood, Jacob Schachter, Gregory A Daniels, Jessica Hassel, Jonathan Cebon, Winald Gerritsen, Victoria Atkinson, Luc Thomas, John McCaffrey, Derek Power, Dana Walker, Rafia Bhore, Joel Jiang, F Stephen Hodi, Jedd D Wolchok
Purpose The addition of nivolumab (anti-programmed death-1 antibody) to ipilimumab (anti-cytotoxic T-cell lymphocyte-associated 4 antibody) in patients with advanced melanoma improves antitumor response and progression-free survival but with a higher frequency of adverse events (AEs). This cross-melanoma study describes the safety profile of the approved nivolumab plus ipilimumab regimen. Methods This retrospective safety review on data from three trials (phase I, II, and III) included patients with advanced melanoma who received at least one dose of nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks × 4 and then nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity while following established guidelines for AE management...
September 15, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28912399/-adoptive-cell-therapy-with-immune-checkpoint-blockade
#6
Atsushi Aruga
Cancer immunotherapy are taking a leading role of cancer therapy due to the development of the immune checkpoint blockade. To date, however, only about 20% of patients have clinical responses and the cancer-specific T cells in cancer site are required to obtain beneficial effects. There has been an innovative development in the field of adoptive cell therapy, especially receptor gene-modified T cells in recent years. The effector cells mostly express PD-1, therefore the cytotoxic reactivity of the effector cells are inhibited by PD-L1...
September 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28912093/lentiviral-gene-delivery-to-plasmolipin-expressing-cells-using-mus-caroli-endogenous-retrovirus-envelope-protein
#7
REVIEW
M M Prokofjeva, G M Proshkina, T D Lebedev, A A Shulgin, P V Spirin, V S Prassolov, S M Deyev
Gene therapy is a promising method for treating malignant diseases. One of the main problems is target delivery of therapeutic genes. Here we show that lentiviral vector particles pseudotyped with Mus caroli endogenous retrovirus (McERV) envelope protein can be used for selective transduction of PLLP-expressing cells. As a therapeutic gene in McERV-pseudotyped vector particles we used miniSOG encoding the cytotoxic FMN-binding protein, which can generate reactive oxygen species under illumination. Significant cytotoxic effect (up to 80% of dead cells in population) was observed in PLLP-expressing cells transduced with McERV-pseudotyped vector particles and subjected to illumination...
September 11, 2017: Biochimie
https://www.readbyqxmd.com/read/28905463/epidemiological-and-clinical-features-of-adult-t-cell-leukemia-lymphoma-atl-in-japan-2010-2011-a-nationwide-survey
#8
Kisato Nosaka, Masako Iwanaga, Yoshitaka Imaizumi, Kenji Ishitsuka, Kenichi Ishizawa, Yoji Ishida, Masahiro Amano, Takashi Ishida, Naokuni Uike, Atae Utsunomiya, Koichi Ohshima, Kazuhiro Kawai, Junji Tanaka, Yoshiki Tokura, Kensei Tobinai, Toshiki Watanabe, Kaoru Uchimaru, Kunihiro Tsukasaki
Adult T-cell leukemia-lymphoma (ATL) is a mature T-cell malignancy associated with human T-cell leukemia virus type I (HTLV-1) infection. Japan is the most endemic country for HTLV-1 and ATL in the world. Recent nationwide studies of Japanese blood donors reported that HTLV-1 carriers spread from endemic areas to non-endemic areas. Therefore, the latest information on nationwide epidemiological and clinical data for ATL is necessary to guide clinical practice. We conducted a multicenter, hospital-based survey of newly diagnosed ATL patients from 2010 to 2011...
September 14, 2017: Cancer Science
https://www.readbyqxmd.com/read/28904745/genome-editing-of-the-hiv-co-receptors-ccr5-and-cxcr4-by-crispr-cas9-protects-cd4-t-cells-from-hiv-1-infection
#9
Zhepeng Liu, Shuliang Chen, Xu Jin, Qiankun Wang, Kongxiang Yang, Chenlin Li, Qiaoqiao Xiao, Panpan Hou, Shuai Liu, Shaoshuai Wu, Wei Hou, Yong Xiong, Chunyan Kong, Xixian Zhao, Li Wu, Chunmei Li, Guihong Sun, Deyin Guo
BACKGROUND: The main approach to treat HIV-1 infection is combination antiretroviral therapy (cART). Although cART is effective in reducing HIV-1 viral load and controlling disease progression, it has many side effects, and is expensive for HIV-1 infected patients who must remain on lifetime treatment. HIV-1 gene therapy has drawn much attention as studies of genome editing tools have progressed. For example, zinc finger nucleases (ZFN), transcription activator like effector nucleases (TALEN) and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 have been utilized to successfully disrupt the HIV-1 co-receptors CCR5 or CXCR4, thereby restricting HIV-1 infection...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28903456/tumor-reductive-therapies-and-antitumor-immunity
#10
REVIEW
Huiqin Guo, Kangla Tsung
Tumor reductive therapy is to reduce tumor burden through direct killing of tumor cells. So far, there is no report on the connection between antitumor immunity and tumor reductive therapies. In the last few years, a new category of cancer treatment, immunotherapy, emerged and they are categorized separately from classic cytotoxic treatments (chemo and radiation therapy). The most prominent examples include cellular therapies (LAK and CAR-T) and immune checkpoint inhibitors (anti-PD-1 and CTLA-4). Recent advances in clinical immunotherapy and our understanding of the mechanism behind them revealed that these therapies have a closer relationship with classic cancer treatments than we thought...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28901740/inhibiting-metastasis-and-preventing-tumor-relapse-by-triggering-host-immunity-with-tumor-targeted-photodynamic-therapy-using-photosensitizer-loaded-functional-nanographenes
#11
Xinhe Yu, Duo Gao, Liquan Gao, Jianhao Lai, Chenran Zhang, Yang Zhao, Lijun Zhong, Bing Jia, Fan Wang, Xiaoyuan Chen, Zhaofei Liu
Effective cancer therapy depends not only on destroying the primary tumor but also on conditioning the host immune system to recognize and eliminate residual tumor cells and prevent metastasis. In this study, a tumor integrin αvβ6-targeting peptide (the HK peptide)-functionalized graphene oxide (GO) was coated with a photosensitizer (HPPH). The resulting GO conjugate, GO(HPPH)-PEG-HK, was investigated whether it could destroy primary tumors and boost host antitumor immunity. We found that GO(HPPH)-PEG-HK exhibited significantly higher tumor uptake than GO(HPPH)-PEG and HPPH...
September 18, 2017: ACS Nano
https://www.readbyqxmd.com/read/28901560/erythema-nodosum-like-panniculitis-mimicking-disease-recurrence-a-novel-toxicity-from-immune-checkpoint-blockade-therapy-report-of-two-patients
#12
Michael T Tetzlaff, Amir A Jazaeri, Carlos A Torres-Cabala, Brinda Rao Korivi, Genie A Landon, Priyadharsini Nagarajan, Adrienne Choksi, Leon Chen, Marc Uemura, Phyu P Aung, Adi Diab, Padmanee Sharma, Michael A Davies, Rodabe Amaria, Victor G Prieto, Jonathan L Curry
Immunotherapies targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death 1 (PD-1) receptor and its ligand (PD-L1) have demonstrated substantial clinical benefit in patients with clinically advanced solid malignancies. However, autoimmune toxicities are common and often significant adverse events with these agents. While rash and pruritus remain the most common cutaneous complications in treated patients, novel dermatologic toxicities related to immune checkpoint blockade continue to emerge as the number of patients exposed to immunotherapy increases...
September 13, 2017: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/28900461/effects-of-wannachawee-recipe-with-antipsoriatic-activity-on-suppressing-inflammatory-cytokine-production-in-hacat-human-keratinocytes
#13
Mingkwan Na Takuathung, Ariyaphong Wongnoppavich, Pornsiri Pitchakarn, Ampai Panthong, Parirat Khonsung, Natthakarn Chiranthanut, Noppamas Soonthornchareonnon, Seewaboon Sireeratawong
Psoriasis is a chronic inflammatory and immune-mediated skin disease. The pathogenesis involves T cells activation via the IL-23/Th17 axis. Conventional treatments of psoriasis have adverse events influencing patients' adherence. Wannachawee Recipe (WCR) has been effectively used as Thai folk remedy for psoriasis patients; however, preclinical evidence defining how WCR works is still lacking. This study defined mechanisms for its antiproliferation and anti-inflammatory effects in HaCaT cells. The cytotoxicity and antiproliferation results from SRB and CCK-8 assays showed that WCR inhibited the growth and viability of HaCaT cells in a concentration-dependent manner...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28898532/immunological-efficacy-of-herbal-medicines-in-prostate-cancer-patients-treated-by-personalized-peptide-vaccine
#14
Noriko Koga, Fukuko Moriya, Kayoko Waki, Akira Yamada, Kyogo Itoh, Masanori Noguchi
This randomized phase II study investigated the immunological efficacy of herbal medicines (HMs) using Hochu-ekki-to and Keishi-bukuryo-gan in combination with personalized peptide vaccination (PPV) for castration-resistant prostate cancer (CRPC). Seventy patients with CRPC were assigned to two arms; PPV plus HMs or PPV alone. Two to four peptides were chosen from 31 peptides derived from cancer antigens for the eight-time subcutaneous injection of PPV according to the patient's human leukocyte antigen type and levels of antigen-specific immunoglobulin G (IgG) titer before PPV treatment...
September 12, 2017: Cancer Science
https://www.readbyqxmd.com/read/28895423/distribution-of-the-most-common-polymorphisms-in-tyms-gene-in-slavic-population-of-central-europe
#15
A Pastorakova, D Chandogova, J Chandoga, J Luha, D Bohmer, J Malova, T Braxatorisova, M Juhosova, S Reznakova, R Petrovic
Thymidylate synthetase (TS) plays a critical role in the de novo synthesis of dTMP inside the cell. Therefore, TS is a suitable target for cytotoxic drugs such as fluoropyrimidines. Drug efficacy and toxicity depend on the intracellular level of TS, which is significantly influenced by the polymorphisms in the 5'UTR (TSER - rs45445694, TSER*3G>C - rs2853542) and 3'UTR (1494del TTAAAG - rs151264360) of TYMS gene. Polymorphic variants of TYMS gene affect TS activity via gene expression and transcript stability...
September 12, 2017: Neoplasma
https://www.readbyqxmd.com/read/28893294/hiv-i-nef-inhibitors-a-novel-class-of-hiv-specific-immune-adjuvants-in-support-of-a-cure
#16
REVIEW
Gregory A Dekaban, Jimmy D Dikeakos
The success of many current vaccines relies on a formulation that incorporates an immune activating adjuvant. This will hold true for the design of a successful therapeutic HIV vaccine targeted at controlling reactivated virus following cessation of combined antiretroviral therapy (cART). The HIV accessory protein Nef functions by interfering with HIV antigen presentation through the major histocompatibility complex I (MHC-I) pathway thereby suppressing CD8(+) cytotoxic T cell (CTL)-mediated killing of HIV infected cells...
September 12, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28892775/challenges-and-perspectives-in-the-immunotherapy-of-hodgkin-lymphoma
#17
REVIEW
Jean-Marie Michot, Julien Lazarovici, David Ghez, Alina Danu, Christophe Fermé, Amélie Bigorgne, Vincent Ribrag, Aurélien Marabelle, Sandrine Aspeslagh
Hodgkin lymphoma (HL) was one of the first few cancers to be cured first with radiotherapy alone and then with a combination of chemotherapy and radiotherapy. Around 80% of the patients with HL will be cured by first-line therapy. However, the ionising radiation not only produces cytotoxicity but also induces alterations in the microenvironment, and patients often struggle with the long-term consequences of these treatments, such as cardiovascular disorders, lung diseases and secondary malignancies. Hence, it is essential to improve treatments while avoiding delayed side-effects...
September 8, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28892752/graphene-quantum-dots-suppress-proinflammatory-t-cell-responses-via-autophagy-dependent-induction-of-tolerogenic-dendritic-cells
#18
Sergej Tomić, Kristina Janjetović, Dušan Mihajlović, Marina Milenković, Tamara Kravić-Stevović, Zoran Marković, Biljana Todorović-Marković, Zdenko Spitalsky, Matej Micusik, Dragana Vučević, Miodrag Čolić, Vladimir Trajković
Graphene quantum dots (GQD) are atom-thick nanodimensional carbon sheets with excellent physico-chemical and biological properties, making them attractive for application in theranostics. However, their immunoregulatory properties are insufficiently investigated, especially in human primary immune cells. We found that non-toxic doses of GQD inhibit the production of proinflammatory and T helper (Th)1 cytokines, and augment the production of anti-inflammatory and Th2 cytokines by human peripheral blood mononuclear cells...
August 29, 2017: Biomaterials
https://www.readbyqxmd.com/read/28890844/evaluation-of-silicon-phthalocyanine-4-photodynamic-therapy-against-human-cervical-cancer-cells-in-vitro-and-in-mice
#19
Jill A Gadzinski, Jianxia Guo, Brian J Philips, Per Basse, Ethan K Craig, Lisa Bailey, John T Comerci, Julie L Eiseman
BACKGROUND: Cervical cancer is the second most common cancer in women worldwide [1]. Photodynamic therapy has been used for cervical intraepithelial neoplasia with good responses, but few studies have used newer phototherapeutics. We evaluated the effectiveness of photodynamic therapy using Pc 4 in vitro and in vivo against human cervical cancer cells. METHODS: CaSki and ME-180 cancer cells were grown as monolayers and spheroids. Cell growth and cytotoxicity were measured using a methylthiazol tetrazolium assay...
December 2016: Advances in Biological Chemistry
https://www.readbyqxmd.com/read/28888366/lipopolysaccharides-promote-binding-and-unfolding-of-the-antibacterial-colicin-e3-rrnase-domain
#20
Allan Mills, Franck Duong
Nuclease colicins are antibacterial proteins produced by certain strains of E. coli to reduce competition from rival strains. These colicins are generally organized with an N-terminal transport (T)-domain, a central receptor binding (R)-domain, and a C-terminal cytotoxic nuclease domain. These colicins are always produced in complex with an inhibitory immunity protein, which dissociates prior entrance of the cytotoxic domain in the target cell. How exactly colicins traverse the cell envelope is not understood, yet this knowledge is important for the design of new antibacterial therapies...
September 6, 2017: Biochimica et Biophysica Acta
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