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Adoptive T-Cell Therapy

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https://www.readbyqxmd.com/read/29147628/trial-watch-adoptively-transferred-cells-for-anticancer-immunotherapy
#1
REVIEW
Carole Fournier, François Martin, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi, Lionel Apetoh
Immunotherapies aimed at strengthening immune effector responses against malignant cells are growing at exponential rates. Alongside, the impressive benefits obtained by patients with advanced melanoma who received adoptively transferred tumor-infiltrating lymphocytes (TILs) have encouraged the scientific community to pursue adoptive cell transfer (ACT)-based immunotherapy. ACT involves autologous or allogenic effector lymphocytes that are generally obtained from the peripheral blood or resected tumors, expanded and activated ex vivo, and administered to lymphodepleted patients...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29145974/immunotherapy-for-triple-negative-breast-cancer-existing-challenges-and-exciting-prospects
#2
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/29145885/future-perspectives-in-melanoma-research-melanoma-bridge-napoli-november-30th-3rd-december-2016
#3
Paolo A Ascierto, Sanjiv S Agarwala, Gennaro Ciliberto, Sandra Demaria, Reinhard Dummer, Connie P M Duong, Soldano Ferrone, Silvia C Formenti, Claus Garbe, Ruth Halaban, Samir Khleif, Jason J Luke, Lluis M Mir, Willem W Overwijk, Michael Postow, Igor Puzanov, Paul Sondel, Janis M Taube, Per Thor Straten, David F Stroncek, Jennifer A Wargo, Hassane Zarour, Magdalena Thurin
Major advances have been made in the treatment of cancer with targeted therapy and immunotherapy; several FDA-approved agents with associated improvement of 1-year survival rates became available for stage IV melanoma patients. Before 2010, the 1-year survival were quite low, at 30%; in 2011, the rise to nearly 50% in the setting of treatment with Ipilimumab, and rise to 70% with BRAF inhibitor monotherapy in 2013 was observed. Even more impressive are 1-year survival rates considering combination strategies with both targeted therapy and immunotherapy, now exceeding 80%...
November 16, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29129787/cd38-nad-axis-regulates-immunotherapeutic-anti-tumor-t-cell-response
#4
Shilpak Chatterjee, Anusara Daenthanasanmak, Paramita Chakraborty, Megan W Wyatt, Payal Dhar, Shanmugam Paneer Selvam, Jianing Fu, Jinyu Zhang, Hung Nguyen, Inhong Kang, Kyle Toth, Mazen Al-Homrani, Mahvash Husain, Gyda Beeson, Lauren Ball, Kristi Helke, Shahid Husain, Elizabeth Garrett-Mayer, Gary Hardiman, Meenal Mehrotra, Michael I Nishimura, Craig C Beeson, Melanie Gubbels Bupp, Jennifer Wu, Besim Ogretmen, Chrystal M Paulos, Jeffery Rathmell, Xue-Zhong Yu, Shikhar Mehrotra
Heightened effector function and prolonged persistence, the key attributes of Th1 and Th17 cells, respectively, are key features of potent anti-tumor T cells. Here, we established ex vivo culture conditions to generate hybrid Th1/17 cells, which persisted long-term in vivo while maintaining their effector function. Using transcriptomics and metabolic profiling approaches, we showed that the enhanced anti-tumor property of Th1/17 cells was dependent on the increased NAD(+)-dependent activity of the histone deacetylase Sirt1...
November 8, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/29127315/human-gingiva-derived-mesenchymal-stem-cells-ameliorate-streptozoticin-induced-t1dm-in-mice-via-suppression-of-t-effector-cells-and-up-regulating-treg-subsets
#5
Wei Zhang, Li Zhou, Junlong Dang, Ximei Zhang, Julie Wang, Yanming Chen, Jichao Liang, Dongqing Li, Jilin Ma, Jia Yuan, Weiwen Chen, Homayoun H Zadeh, Nancy Olsen, Song Guo Zheng
There is yet no cure for type 1 diabetes (T1DM) so far. A significant body of evidence has demonstrated that bone marrow-derived mesenchymal stem cells (BMSCs) showed great potential in controlling T1DM. But there exists much difficulty in using BMSCs as a clinical therapy. We here test whether a new population of mesenchymal stem cells from human gingiva (GMSCs), which has many advantages over BMSCs, can delay or prevent progress of T1DM. GMSCs were adoptively transferred to multiple low-dose streptozotocin (STZ)-induced T1DM...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29125868/local-thoracic-therapy-improve-prognosis-for-stage-iv-non-small-cell-lung-cancer-patients-combined-with-chemotherapy-a-surveillance-epidemiology-and-end-results-database-analysis
#6
Kaitai Liu, Dawei Zheng, GuoDong Xu, Zhennan Du, Shibo Wu
Patients with stage IV non-small cell lung cancer (NSCLC) comprise a heterogeneous group, and the optimal treatment for this group of patients is complex and debatable. We aimed to assess the effect of local thoracic therapy combined with chemotherapy on cancer specific survival (CSS). To evaluate the CSS of four subgroups of patients with stage IV NSCLC according to four different treatment modalities: combined modality of Chemotherapy, Surgery, and Radiation (Chem+Sur+RT), Chemotherapy and Radiation (Chem+RT), Chemotherapy and Surgery (Chem+Sur), and Chemotherapy only (Chem Only) by analyzing the Surveillance, Epidemiology, and End Results (SEER)-registered database...
2017: PloS One
https://www.readbyqxmd.com/read/29123521/good-manufacturing-practice-compliant-production-and-lot-release-of-ex-vivo-expanded-regulatory-t-cells-as-basis-for-treatment-of-patients-with-autoimmune-and-inflammatory-disorders
#7
Manuel Wiesinger, Diane Stoica, Susanne Roessner, Carmen Lorenz, Anika Fischer, Raja Atreya, Clemens F Neufert, Imke Atreya, Alexander Scheffold, Beatrice Schuler-Thurner, Markus F Neurath, Gerold Schuler, Caroline J Voskens
In recent years, the exploration of regulatory T cell (Treg)-based cellular therapy has become an attractive strategy to ameliorate inflammation and autoimmunity in various clinical settings. The main obstacle to the clinical application of Treg in human is their low number circulating in peripheral blood. Therefore, ex vivo expansion is inevitable. Moreover, isolation of Treg bears the risk of concurrent isolation of unwanted effector cells, which may trigger or deteriorate inflammation upon adoptive Treg transfer...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29123516/avidity-and-bystander-suppressive-capacity-of-human-regulatory-t-cells-expressing-de-novo-autoreactive-t-cell-receptors-in-type-1-diabetes
#8
Wen-I Yeh, Howard R Seay, Brittney Newby, Amanda L Posgai, Filipa Botelho Moniz, Aaron Michels, Clayton E Mathews, Jeffrey A Bluestone, Todd M Brusko
The ability to alter antigen specificity by T-cell receptor (TCR) or chimeric antigen receptor (CAR) gene transfer has facilitated personalized cellular immune therapies in cancer. Inversely, this approach can be harnessed in autoimmune settings to attenuate inflammation by redirecting the specificity of regulatory T cells (Tregs). Herein, we demonstrate efficient protocols for lentiviral gene transfer of TCRs that recognize type 1 diabetes-related autoantigens with the goal of tissue-targeted induction of antigen-specific tolerance to halt β-cell destruction...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29123081/resistance-to-cancer-immunotherapy-mediated-by-apoptosis-of-tumor-infiltrating-lymphocytes
#9
Jingjing Zhu, Céline G Powis de Tenbossche, Stefania Cané, Didier Colau, Nicolas van Baren, Christophe Lurquin, Anne-Marie Schmitt-Verhulst, Peter Liljeström, Catherine Uyttenhove, Benoit J Van den Eynde
Despite impressive clinical success, cancer immunotherapy based on immune checkpoint blockade remains ineffective in many patients due to tumoral resistance. Here we use the autochthonous TiRP melanoma model, which recapitulates the tumoral resistance signature observed in human melanomas. TiRP tumors resist immunotherapy based on checkpoint blockade, cancer vaccines or adoptive T-cell therapy. TiRP tumors recruit and activate tumor-specific CD8(+) T cells, but these cells then undergo apoptosis. This does not occur with isogenic transplanted tumors, which are rejected after adoptive T-cell therapy...
November 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/29118234/emerging-role-of-car-t-cells-in-non-hodgkin-s-lymphoma
#10
REVIEW
Mauro P Avanzi, Renier J Brentjens
Adoptive T-cell therapy with chimeric antigen receptor T cells (CAR-Ts) has produced impressive clinical responses among patients with B-cell malignancies, and several groups have published positive results using anti-CD19 CAR-Ts for the treatment of B-cell acute lymphoblastic leukemia. Recently, new data from clinical trials have demonstrated the benefits of CAR-T therapy in the non-Hodgkin's lymphoma (NHL) setting. This review describes some of the most recent and promising advances in engineered T-cell therapy, with particular emphasis on the clinical benefits of NHL treatment...
November 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29118005/redirecting-t-cells-to-hematological-malignancies-with-bispecific-antibodies
#11
Mireya Paulina Velasquez, Challice L Bonifant, Stephen Gottschalk
There is a need to improve outcomes for patients with recurrent and/or refractory hematological malignancies. Immunotherapy holds the promise to meet this need since it does not rely on the cytotoxic mechanism of conventional therapies. Among different forms of immunotherapy, redirecting T cells to hematological malignancies with bispecific antibodies (BsAbs) is an attractive strategy. BsAbs are an 'off-the-shelf' product that is easily scalable in contrast to adoptive T-cell therapies. Among these, the bispecific T-cell engager (BiTE) blinatumomab has emerged as the most successful BsAb to date...
November 8, 2017: Blood
https://www.readbyqxmd.com/read/29116089/resistance-to-tgf%C3%AE-suppression-and-improved-anti-tumor-responses-in-cd8-t-cells-lacking-ptpn22
#12
Rebecca J Brownlie, Celine Garcia, Mate Ravasz, Dietmar Zehn, Robert J Salmond, Rose Zamoyska
Transforming growth factor β (TGFβ) is important in maintaining self-tolerance and inhibits T cell reactivity. We show that CD8(+) T cells that lack the tyrosine phosphatase Ptpn22, a major predisposing gene for autoimmune disease, are resistant to the suppressive effects of TGFβ. Resistance to TGFβ suppression, while disadvantageous in autoimmunity, helps Ptpn22 (-/-) T cells to be intrinsically superior at clearing established tumors that secrete TGFβ. Mechanistically, loss of Ptpn22 increases the capacity of T cells to produce IL-2, which overcomes TGFβ-mediated suppression...
November 7, 2017: Nature Communications
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
#13
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/29107016/chimeric-antigen-receptor-car-t-cell-therapy-for-thoracic-malignancies
#14
REVIEW
Stefan Kiesgen, Leonardo Chicaybam, Navin K Chintala, Prasad S Adusumilli
Chimeric antigen receptor (CAR) T cells are patient T cells that are transduced with genetically engineered synthetic receptors to target a cancer cell surface antigen. The remarkable clinical response rates achieved by adoptive transfer of T cells that target CD19 in patients with leukemia and lymphoma have led to a growing number of clinical trials exploring CAR T-cell therapy for solid tumors. Herein, we review the evolution of adoptive T-cell therapy, highlight advances in CAR T-cell therapy for thoracic malignancies, and summarize the targets being investigated in clinical trials for patients with lung cancer, malignant pleural mesothelioma, and esophageal cancer...
October 26, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29105517/car-t-cell-therapy-for-multiple-myeloma-where-are-we-now-and-where-are-we-headed
#15
Arnab Ghosh, Sham Mailankody, Sergio A Giralt, C Ola Landgren, Eric L Smith, Renier J Brentjens
While recent progress has been made in the management of multiple myeloma, it remains a highly fatal malignancy especially among patients with relapsed-refractory disease. Immunotherapy with adoptive T cells targeting myeloma-associated antigens are at various stages of development and have brought about a new hope for cure. This is a review on the emerging field of adoptively transferred engineered T cell based approaches, with an in-depth focus on chimeric antigen receptors (CAR) targeting multiple myeloma...
November 6, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29104081/wnt-pathway-activator-tws119-enhances-the-proliferation-and-cytolytic-activity-of-human-%C3%AE-%C3%AE-t-cells-against-colon-cancer
#16
Yong-Qiang Chen, Lu Zheng, Mohanad Aldarouish, Zhong-Hai Zhou, Ning Pan, Jun-Quan Liu, Fu-Xing Chen, Li-Xin Wang
γδT cells are a distinct T-cell subset that display unique characteristics regarding T-cell receptor gene usage, tissue tropism and antigen recognition. Adoptive γδT cell transfer therapy has recently been gaining importance as an efficient approach in cancer immunotherapy. However, exploiting γδT cell response for tumour immunotherapy is a challenge due to cell numbers, activities and differentiation states that minimize the clinical therapeutic effects. Previous studies have indicated that the wnt/β-catenin signalling pathway plays a crucial role in the differentiation, survival and enhancement of the immune response of T lymphocytes...
November 2, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29103317/anticancer-cellular-immunotherapies-derived-from-umbilical-cord-blood
#17
Katalin Balassa, Vanderson Rocha
Introduction The lack of highly effective drugs in many malignancies has prompted scientific interest in the development of alternative treatment strategies. Cellular immunotherapy involving the adoptive transfer of immune cells that potently recognize and eliminate malignantly transformed cells has become a promising new tool in the anticancer armory. Studies suggest that the unique biological properties of umbilical cord blood (UCB) cells could precipitate enhanced anticancer activity; hence, UCB could be an optimal source for immunotherapy with the potential to provide products with "off-the-shelf" availability...
November 6, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29093083/dynamics-of-sendai-virus-spread-clearance-and-immunotherapeutic-efficacy-after-hematopoietic-cell-transplant-imaged-non-invasively-in-mice
#18
Heba H Mostafa, Peter Vogel, Ashok Srinivasan, Charles J Russell
There are no approved vaccines or virus-specific treatments for human parainfluenza viruses (PIVs), which have recently been reclassified into species human respirovirus 1 and 3 and human rubulavirus 2 and 4 These viruses cause morbidity and mortality in immunocompromised patients including those undergoing hematopoietic cell transplant (HCT). No small-animal models exist for non-invasive imaging of respiratory viral infection in the HCT host despite the utility such a system would offer to monitor prolonged infection, its clearance, and treatment options...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29093005/dendritic-cells-enhance-polyfunctionality-of-adoptively-transferred-t-cells-which-target-cytomegalovirus-in-glioblastoma
#19
Elizabeth Reap, Carter M Suryadevara, Kristen A Batich, Luis Sanchez-Perez, Gary E Archer, Robert J Schmittling, Pamela K Norberg, James E Herndon, Patrick Healy, Kendra L Congdon, Patrick C Gedeon, Olivia C Campbell, Adam M Swartz, Katherine A Riccione, John S Yi, Mohammed K Hossain-Ibrahim, Anirudh Saraswathula, Smita K Nair, Anastasie M Dunn-Pirio, Taylor M Broome, Kent J Weinhold, Annick Desjardins, Gordana Vlahovic, Roger Mclendon, Allan H Friedman, Henry S Friedman, Darell D Bigner, Peter E Fecci, Duane A Mitchell, John H Sampson
Median survival for glioblastoma (GBM) remains <15 months. Human Cytomegalovirus (CMV) antigens have been identified in GBM but not normal brain, providing an unparalleled opportunity to subvert CMV antigens as tumor-specific immunotherapy targets. A recent trial in recurrent GBM patients demonstrated the potential clinical benefit of adoptive T cell therapy (ATCT) of CMV phosphoprotein 65 (pp65)-specific T cells. However, ex vivo analyses from this study found no change in the capacity of CMV pp65-specific T cells to gain multiple effector functions or polyfunctionality, which has been associated with superior antitumor efficacy...
November 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/29091870/immunotherapy-for-acute-myeloid-leukemia-aml-a-potent-alternative-therapy
#20
REVIEW
Desmond O Acheampong, Christian K Adokoh, Du-Bois Asante, Ernest A Asiamah, Prince A Barnie, Dan O M Bonsu, Foster Kyei
The standard therapy of AML for many years has been chemotherapy with or without stem transplantation. However, there has not been any tangible improvement in this treatment beyond induction through chemotherapy and consolidation with allogeneic stem cell transplantation or chemotherapy. Residual AML cells which later cause relapse mostly persist even after rigorous standard therapy. It is imperative therefore to find an alternative therapy that can take care of the residual AML cells. With a better understanding of how the immune system works to destroy tumor cells and inhibit their growth, another therapeutic option immunotherapy has emerged to address the difficulties associated with the standard therapy...
October 26, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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