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Adoptive immunotherapy

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https://www.readbyqxmd.com/read/28198830/-final-common-pathway-of-human-cancer-immunotherapy-targeting-random-somatic-mutations
#1
REVIEW
Eric Tran, Paul F Robbins, Steven A Rosenberg
Effective clinical cancer immunotherapies, such as administration of the cytokine IL-2, adoptive cell transfer (ACT) and the recent success of blockade of the checkpoint modulators CTLA-4 and PD-1, have been developed without clear identification of the immunogenic targets expressed by human cancers in vivo. Immunotherapy of patients with cancer through the use of ACT with autologous lymphocytes has provided an opportunity to directly investigate the antigen recognition of lymphocytes that mediate cancer regression in humans...
February 15, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28197365/crispr-cas9-mediated-disruption-of-pd-1-on-human-t-cells-for-adoptive-cellular-therapies-of-ebv-positive-gastric-cancer
#2
Shu Su, Zhengyun Zou, Fangjun Chen, Naiqing Ding, Juan Du, Jie Shao, Lin Li, Yao Fu, Bian Hu, Yang Yang, Huizi Sha, Fanyan Meng, Jia Wei, Xingxu Huang, Baorui Liu
The successful use of immune cell checkpoint inhibitors PD-1 and PD-L1, over the past 5 y has raised the concern of using immunotherapy to treat various cancers. Epstein-Barr virus-associated gastric cancer (EBVaGC) exhibits high infiltration of lymphocytes and high amplification of immune-related genes including PD-L1 as distinguished from Epstein-Barr virus-non-associated gastric cancer (EBVnGC). Here, we presume that this PD-1/PD-L1 pathway may hinder the efficacy of adoptive T cell therapy toward EBVaGC...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28193627/adoptive-transfer-of-invariant-nkt-cells-as-immunotherapy-for-advanced-melanoma-a-phase-1-clinical-trial
#3
Mark A Exley, Philip Friedlander, Nadia Alatrakchi, Lianne Vriend, Simon C Yue, Tetsuro Sasada, Wanyong Zang, Yo Mizukami, Justice Clark, David Nemer, Ken LeClair, Christine Canning, Heather Daley, Glenn Dranoff, Anita Giobbie-Hurder, F Stephen Hodi, Jerome Ritz, Steven P Balk
PURPOSE: Invariant NKT cells (iNKT) are innate-like CD1d-restricted T cells with immunoregulatory activity in diseases including cancer. iNKT from advanced cancer patients can have reversible defects including IFNγ production, and iNKT IFNγ production may stratify for survival. Previous clinical trials using iNKT cell activating ligand α-galactosylceramide have shown responses. Therefore, a phase 1 clinical trial was performed of autologous in vitro expanded iNKT cells in stage IIIB-IV melanoma...
February 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28184969/augmented-anti-tumor-activity-of-nk-92-cells-expressing-chimeric-receptors-of-tgf-%C3%AE-r-ii-and-nkg2d
#4
Zhongjuan Wang, Linghua Guo, Yuan Song, Yinsheng Zhang, Dandan Lin, Bo Hu, Yu Mei, Dedy Sandikin, Haiyan Liu
The capacity of natural killer (NK) cells to kill tumor cells without specific antigen recognition provides an advantage over T cells and makes them potential effectors for tumor immunotherapy. However, the efficacy of NK cell adoptive therapy can be limited by the immunosuppressive tumor microenvironment. Transforming growth factor-β (TGF-β) is a potent immunosuppressive cytokine that can suppress NK cell function. To convert the suppressive signal induced by TGF-β to an activating signal, we genetically modified NK-92 cells to express a chimeric receptor with TGF-β type II receptor extracellular and transmembrane domains and the intracellular domain of NK cell-activating receptor NKG2D (TN chimeric receptor)...
February 9, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28166468/dose-finding-designs-for-trials-of-molecularly-targeted-agents-and-immunotherapies
#5
Cody Chiuzan, Jonathan Shtaynberger, Gulam A Manji, Jimmy K Duong, Gary K Schwartz, Anastasia Ivanova, Shing M Lee
Recently, there has been a surge of early phase trials of molecularly targeted agents (MTAs) and immunotherapies. These new therapies have different toxicity profiles compared to cytotoxic therapies. MTAs can benefit from new trial designs that allow inclusion of low-grade toxicities, late-onset toxicities, addition of an efficacy endpoint, and flexibility in the specification of a target toxicity probability. To study the degree of adoption of these methods, we conducted a Web of Science search of articles published between 2008 and 2014 that describe phase 1 oncology trials...
February 6, 2017: Journal of Biopharmaceutical Statistics
https://www.readbyqxmd.com/read/28166182/vogt-koyanagi-harada-like-syndrome-complicating-pembrolizumab-treatment-for-metastatic-melanoma
#6
Marion Bricout, Adeline Petre, Mona Amini-Adle, Widad Bezza, Pascal Seve, Laurent Kodjikian, Stéphane Dalle, Luc Thomas
Vogt-Koyanagi-Harada (VKH) syndrome is a rare condition implicating systemic immune reaction against melanocytes. The pathophysiology is unclear. A genetic predisposition has been suggested as HLA-DR4/DRB1*04 is more common among VKH patients. Drug induced VKH syndrome has been reported in advanced melanoma patients receiving immunotherapy, including ipilimumab and adoptive cell transfer of Tumor-Infiltrating Lymphocyte associated with IL-2. To date, no case of anti PD-1 -induced VKH syndrome has been described...
February 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28162915/simple-in-vitro-generation-of-human-leukocyte-antigen-g-expressing-t-regulatory-cells-through-pharmacological-hypomethylation-for-adoptive-cellular-immunotherapy-against-graft-versus-host-disease
#7
Panagiota Stamou, Dimitra Marioli, Alexandra L Patmanidi, Argyro Sgourou, Angeliki Vittoraki, Efthymia Theofani, Chryso Pierides, Stavros Taraviras, Paul A Costeas, Alexandros Spyridonidis
BACKGROUND: Major barriers in using classical FOXP3+ regulatory T cells (Tregs) in clinical practice are their low numbers in the circulation, the lack of specific cell surface markers for efficient purification and the loss of expression of Treg signature molecules and suppressive function after in vitro expansion or in a pro-inflammatory microenviroment. A surface molecule with potent immunosuppressive function is the human leukocyte antigen-G (HLA-G), which is normally expressed in placenta protecting the "semi-allogeneic" fetus from maternal immune attack...
February 2, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28162024/immunotherapeutic-strategies-for-the-treatment-of-renal-cell-carcinoma-where-will-we-go
#8
Inês Anselmo da Costa, Steffen Rausch, Stephan Kruck, Tilman Todenhöfer, Arnulf Stenzl, Jens Bedke
Historically, renal cell carcinoma (RCC) is considered a chemotherapy-resistant tumor. The cornerstone of systemic therapy included mammalian target of rapamycin (mTOR) inhibitors, endothelial growth factor receptor (VEGFR) and tyrosine kinase inhibitors (TKIs). Currently, a new era is enteres with promising immunotherapeutic treatments, which are becoming commercially available. Areas covered: We provide a comprehensive review using PubMed and ClinicalTrials.gov about the following immunotherapies in RCC: i) vaccine therapy, ii) adoptive T Cell Transfer and CAR T cells, iii) nonspecific immunotherapy-IL-2 (new formulations), iv) Checkpoint inhibitors, v) other checkpoint-molecules...
February 4, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28150213/artificial-antigen-presenting-cells-for-immunotherapies
#9
Alyssa L Siefert, Tarek M Fahmy, Dongin Kim
Artificial antigen-presenting cells (aAPCs) overcome many of the limitations of biologically based adoptive immunotherapy protocols. While these acellular systems can be designed with a variety of parameters, including material type, diameter, and proliferative signals for T cells, we outline methods to formulate and characterize a comprehensive polymeric microparticle aAPC platform. These aAPCs, which can be reproducibly fabricated in large quantities, efficiently stimulate antigen-specific T cell activation and proliferation by both paracrine cytokine signals and engagement of T cell surface proteins...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28147310/colorectal-cancer-cells-suppress-cd4-t-cells-immunity-through-canonical-wnt-signaling
#10
Xuan Sun, Suoning Liu, Daguang Wang, Yang Zhang, Wei Li, Yuchen Guo, Hua Zhang, Jian Suo
Understanding how colorectal cancer escapes from immunosurveillance and immune attack is important for developing novel immunotherapies for colorectal cancer. In this study we evaluated the role of canonical Wnt signaling in the regulation of T cell function in a mouse colorectal cancer model. We found that colorectal cancer cells expressed abundant Wnt ligands, and intratumoral T cells expressed various Frizzled proteins. Meanwhile, both active β-catenin and total β-catenin were elevated in intratumoral T cells...
January 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28146052/expansion-of-t-cells-with-interleukin-21-for-adoptive-immunotherapy-of-murine-mammary-carcinoma
#11
Christine K Zoon, Wen Wan, Laura Graham, Harry D Bear
We previously demonstrated that culturing antigen-sensitized draining lymph node (DLN) lymphocytes from BALB/c mice in interleukin (IL)-7/15 after activation with bryostatin/ionomycin (B/I) is superior to culture in IL-2 for expansion, differentiation to cluster of differentiation (CD)8+ cells and anti-tumor activity. We sought to determine whether the substitution or addition of IL-21 to culture had a similar effect. DLN lymphocytes were antigen-sensitized with 4T1 mammary carcinoma 10 days prior to harvest, activated with B/I, and expanded in culture for 7 days with either IL-2, IL-21, IL-2/21, IL-7/15, or IL-7/15/21...
January 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28140447/myeloid-derived-suppressor-cells-mediate-tolerance-induction-in-autoimmune-disease
#12
Anja Wegner, Johan Verhagen, David C Wraith
In multiple sclerosis (MS) T cells aberrantly recognise self-peptides of the myelin sheath and attack the central nervous system (CNS). Antigen-specific peptide immunotherapy, which aims to restore tolerance while avoiding the use of non-specific immunosuppressive drugs, is a promising approach to combat autoimmune disease, but the cellular mechanisms behind successful therapy remain poorly understood. Myeloid-derived suppressor cells (MDSCs) have been studied intensively in the field of cancer and to a lesser extent in autoimmunity...
January 31, 2017: Immunology
https://www.readbyqxmd.com/read/28138559/transient-stimulation-expands-superior-antitumor-t-cells-for-adoptive-therapy
#13
Yuki Kagoya, Munehide Nakatsugawa, Toshiki Ochi, Yuchen Cen, Tingxi Guo, Mark Anczurowski, Kayoko Saso, Marcus O Butler, Naoto Hirano
Adoptive cell therapy is a potentially curative therapeutic approach for patients with cancer. In this treatment modality, antitumor T cells are exponentially expanded in vitro prior to infusion. Importantly, the results of recent clinical trials suggest that the quality of expanded T cells critically affects their therapeutic efficacy. Although anti-CD3 mAb-based stimulation is widely used to expand T cells in vitro, a protocol to generate T cell grafts for optimal adoptive therapy has yet to be established...
January 26, 2017: JCI Insight
https://www.readbyqxmd.com/read/28138156/antibody-dependent-cell-cytotoxicity-adcc-immunotherapy-strategies-enhancing-effector-nk-cells
#14
REVIEW
Maria Carmen Ochoa, Luna Minute, Inmaculada Rodriguez, Saray Garasa, Elisabeth Perez-Ruiz, Susana Inogés, Ignacio Melero, Pedro Berraondo
Antibody-dependent cellular cytotoxicity (ADCC) is a set of mechanisms that target cells coated with IgG antibodies of the proper subclasses (IgG1 in the human) to be the prey of cell-to-cell cytolysis executed by immune cells expressing FcRIIIA (CD16A). These effectors include not only NK cells but also other CD16(+) subsets such as monocyte/macrophages, NKT cells or γδ T cells. In cancer therapy, ADCC is exploited by antibodies that selectively recognize proteins on the surface of malignant cells. An approach to enhance antitumor activity is to act on effector cells so they are increased in their numbers or enhanced in their individual (on a cell per cell basis) ADCC performance...
January 31, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28137717/differentiated-state-of-initiating-tumor-cells-is-key-to-distinctive-immune-responses-seen-in-h-rasg12v-induced-squamous-tumors
#15
Michael A Podolsky, Jacob T Bailey, Andrew J Gunderson, Carrie J Oakes, Kyle Breech, Adam B Glick
Heterogeneity in tumor immune responses is a poorly understood yet critical parameter for successful immunotherapy. In two doxycycline-inducible models where oncogenic H-Ras(G12V) is targeted either to the epidermal basal/stem cell layer with a Keratin14-rtTA transgene (K14Ras), or committed progenitor/suprabasal cells with an Involucrin-tTA transgene (InvRas) we observed strikingly distinct tumor immune responses. On threshold doxycycline levels yielding similar Ras expression, tumor latency, and numbers, tumors from K14Ras mice had an immunosuppressed microenvironment while InvRas tumors had a pro-inflammatory microenvironment...
January 30, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28129121/masked-chimeric-antigen-receptor-for-tumor-specific-activation
#16
Xiaolu Han, Paul D Bryson, Yifan Zhao, Gunce E Cinay, Si Li, Yunfei Guo, Natnaree Siriwon, Pin Wang
Adoptive cellular therapy based on chimeric antigen receptor (CAR)-engineered T (CAR-T) cells is a powerful form of cancer immunotherapy. CAR-T cells can be redirected to specifically recognize tumor-associated antigens (TAAs) and induce high levels of antitumor activity. However, they may also display "on-target off-tumor" toxicities, resulting from low-level expression of TAAs in healthy tissues. These adverse effects have raised considerable safety concerns and limited the clinical application of this otherwise promising therapeutic modality...
January 4, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28128715/adoptive-cell-therapy-past-present-and-future
#17
Jonathan E Cohen, Sharon Merims, Stephen Frank, Roni Engelstein, Tamar Peretz, Michal Lotem
The immune system is a potent inhibitor of tumor growth with curative potential, constituting in many eyes the future of antineoplastic therapy. Adoptive cell therapy (ACT) is a form of immunotherapy in which autologous cancer-cognate lymphocytes are expanded and modified ex vivo and re-infused to combat the tumor. This review follows the evolvement of ACT and treatment protocols, focusing on unresolved dilemmas regarding this treatment while providing evidence for its effectiveness in refractory patients. Future directions of ACT are discussed, in particular with regard to genetic engineering of autologous cells, and the role of ACT in the era of checkpoint inhibitors is addressed...
January 2017: Immunotherapy
https://www.readbyqxmd.com/read/28122453/improving-t-cell-expansion-with-a-soft-touch
#18
Lester H Lambert, Geraldine K E Goebrecht, Sarah E De Leo, Roddy S O'Connor, Selene Nunez-Cruz, Tai-De Li, Jinglun Yuan, Michael C Milone, Lance C Kam
Protein-coated microbeads provide a consistent approach for activating and expanding populations of T cells for immunotherapy but do not fully capture the properties of antigen presenting cells. In this report, we enhance T cell expansion by replacing the conventional, rigid bead with a mechanically soft elastomer. Polydimethylsiloxane (PDMS) was prepared in a microbead format and modified with activating antibodies to CD3 and CD28. A total of three different formulations of PDMS provided an extended proliferative phase in both CD4(+)-only and mixed CD4(+)-CD8(+) T cell preparations...
January 30, 2017: Nano Letters
https://www.readbyqxmd.com/read/28121247/targeting-inos-to-increase-efficacy-of-immunotherapies
#19
Suhendan Ekmekcioglu, Elizabeth A Grimm, Jason Roszik
Inducible NO synthase (iNOS/NOS2) protein expression is a well-studied predictor of poor outcome in multiple cancers, and it has also been associated with inflammatory and immunosuppressive processes in the tumor microenvironment. Immunotherapies are becoming increasingly key components in cancer treatment, and iNOS is receiving more attention as a potential regulator of treatment resistance. As we have reported in pancreatic cancer, by modulation of effector T-cell activity, iNOS overexpression may allow the tumor to escape the immune response through creating a microenvironment which causes recalcitrance to immunotherapy...
January 25, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28116637/adoptive-t-cell-immunotherapy-for-patients-with-primary-immunodeficiency-disorders
#20
REVIEW
Lauren P McLaughlin, Catherine M Bollard, Michael Keller
Primary immunodeficiency disorders (PID) are a group of inborn errors of immunity with a broad range of clinical severity but often associated with recurrent and serious infections. While hematopoietic stem cell transplantation (HSCT) can be curative for some forms of PID, chronic and/or refractory viral infections remain a cause of morbidity and mortality both before and after HSCT. Although antiviral pharmacologic agents exist for many viral pathogens, these are associated with significant costs and toxicities and may not be effective for increasingly drug-resistant pathogens...
January 2017: Current Allergy and Asthma Reports
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