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adoptive cell therapy

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https://www.readbyqxmd.com/read/28526681/adoptive-transfer-of-phosphoantigen-specific-%C3%AE-%C3%AE-t-cell-subset-attenuates-mycobacterium-tuberculosis-infection-in-nonhuman-primates
#1
Arwa Qaqish, Dan Huang, Crystal Y Chen, Zhuoran Zhang, Richard Wang, Shengpu Li, Enzhuoa Yang, Yang Lu, Michelle H Larsen, William R Jacobs, Lixia Qian, James Frencher, Ling Shen, Zheng W Chen
The dominant Vγ2Vδ2 T cell subset recognizes phosphoantigen and exists only in humans and nonhuman primates. Despite the discovery of γδ T cells >30 y ago, a proof-of-concept study has not been done to prove the principle that the Vγ2Vδ2 T cell subset is protective against Mycobacterium tuberculosis and other infections. In this study, we used an adoptive cell-transfer strategy to define the protective role of Vγ2Vδ2 T cells in a primate tuberculosis (TB) model. Vγ2Vδ2 T cells for adoptive transfer displayed central/effector memory and mounted effector functions, including the production of anti-M...
May 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28522749/expansion-of-tumor-infiltrating-cd8-t-cells-expressing-pd-1-improves-the-efficacy-of-adoptive-t-cell-therapy
#2
Sarita M Fernandez-Poma, Diego Salas-Benito, Teresa Lozano, Noelia Casares, José-Ignacio Riezu-Boj, Uxua Mancheño, Edurne Elizalde, Diego Alignani, Natalia Zubeldia, Itziar Otano, Enrique Conde, Pablo Sarobe, Juan J Lasarte, Sandra Hervas-Stubbs
Recent studies have found that tumor-infiltrating lymphocytes (TIL) expressing PD-1 can recognize autologous tumor cells, suggesting that cells derived from PD-1+ TIL can be used in adoptive T cell therapy (ACT). However, no study thus far has evaluated the antitumor activity of PD-1-selected TIL in vivo. In two mouse models of solid tumors, we show that PD-1 allows identification and isolation of tumor-specific TIL without previous knowledge of their antigen specificities. Importantly, despite the high proportion of tumor-reactive T cells present in bulk CD8 TIL before expansion, only T cell products derived from sorted PD-1+, but not from PD-1- or bulk CD8 TIL, specifically recognized tumor cells...
May 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28522193/ph-triggered-re-assembly-of-nanosphere-to-nanofiber-the-role-of-peptide-conformational-change-for-enhanced-cancer-therapy
#3
Peiqing Liang, Junjiong Zheng, Shulin Dai, Jiayu Wang, Zhaoqing Zhang, Ting Kang, Changyun Quan
pH-triggered conformational change and subsequent re-assembly of nanostructures provide a new strategy in nanomedicine for controlled drug release and enhanced therapy. Here, we reported the development of a novel pH-responsive nano-assembly as a drug carrier from peptide amphiphile (PA) consisting of mimicking peptide and stearic acid moieties. The mimicking peptide is a basic 17-amino acid peptide derived from antennapedia homeodomain, and undergoes a conformational transition of the secondary structure from β-sheet at pH7...
May 15, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28515922/primary-primitive-neuroectodermal-tumor-of-the-cervix-a-report-of-two-cases-and-review-of-the-literature
#4
Xiaofeng Wang, Yan Gao, Yanning Xu, Yixin Liu, Pengpeng Qu
Peripheral primitive neuroectodermal tumor (PNET) of the cervix uteri is extremely rare. Two cases of PNET of the cervix are presented herein. Two female patients, aged 48 and 43 years, presented with irregular uterine bleeding over the course of 1 year, and increased urinary frequency for 1 month, respectively. On gynecological examination, a mass in the cervix was palpated and a biopsy performed. The findings of the initial biopsy revealed small-cell carcinoma in both patients. Following neoadjuvant chemotherapy and radiotherapy, radical hysterectomy was performed in both patients...
May 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28510446/modularly-constructed-synthetic-granzyme-b-molecule-enables-interrogation-of-intracellular-proteases-for-targeted-cytotoxicity
#5
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 16, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28507811/adoptive-natural-killer-cell-therapy-is-effective-in-reducing-pulmonary-metastasis-of-ewing-sarcoma
#6
Alexander A Tong, Hasan Hashem, Saada Eid, Frederick Allen, Daniel Kingsley, Alex Y Huang
The survival of patients with metastatic or relapsed Ewing sarcoma (ES) remains dismal despite intensification of combination chemotherapy and radiotherapy, precipitating the need for novel alternative therapies with minimal side effects. Natural killer (NK) cells are promising additions to the field of cellular immunotherapy. Adoptive NK cell therapy has shown encouraging results in hematological malignancies. Despite these initial promising successes, however, NK cell therapy for solid tumors remains to be investigated using in vivo tumor models...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507809/t-cell-therapy-targeting-a-public-neoantigen-in-microsatellite-instable-colon-cancer-reduces-in-vivo-tumor-growth
#7
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/28507788/adaptive-t-cell-responses-induced-by-oncolytic-herpes-simplex-virus-granulocyte-macrophage-colony-stimulating-factor-therapy-expanded-by-dendritic-cell-and-cytokine-induced-killer-cell-adoptive-therapy
#8
Jun Ren, William R Gwin, Xinna Zhou, Xiaoli Wang, Hongyan Huang, Ni Jiang, Lei Zhou, Pankaj Agarwal, Amy Hobeika, Erika Crosby, Zachary C Hartman, Michael A Morse, Kevin H Eng, H Kim Lyerly
Purpose: Although local oncolytic viral therapy (OVT) may enhance tumor lysis, antigen release, and adaptive immune responses, systemic antitumor responses post-therapy are limited. Adoptive immunotherapy with autologous dendritic cells (DC) and cytokine-induced killer cells (DC-CIK) synergizes with systemic therapies. We hypothesized that OVT with Herpes Simplex Virus-granulocyte macrophage-colony-stimulating factor (HSV-GM-CSF) would induce adaptive T cell responses that could be expanded systemically with sequential DC-CIK therapy...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28506464/recruited-monocytes-and-type-2-immunity-promote-lung-regeneration-following-pneumonectomy
#9
Andrew J Lechner, Ian H Driver, Jinwoo Lee, Carmen M Conroy, Abigail Nagle, Richard M Locksley, Jason R Rock
To investigate the role of immune cells in lung regeneration, we used a unilateral pneumonectomy model that promotes the formation of new alveoli in the remaining lobes. Immunofluorescence and single-cell RNA sequencing found CD115+ and CCR2+ monocytes and M2-like macrophages accumulating in the lung during the peak of type 2 alveolar epithelial stem cell (AEC2) proliferation. Genetic loss of function in mice and adoptive transfer studies revealed that bone marrow-derived macrophages (BMDMs) traffic to the lung through a CCL2-CCR2 chemokine axis and are required for optimal lung regeneration, along with Il4ra-expressing leukocytes...
May 3, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28506131/new-drugs-and-allogeneic-hematopoietic-cell-transplantation-for-hematological-malignancies-do-they-have-a-role-in-bridging-consolidating-or-conditioning-transplantation-treatment
#10
Francesca Patriarca, Luisa Giaccone, Francesco Onida, Luca Castagna, Barbara Sarina, Vittorio Montefusco, Alberto Mussetti, Nicola Mordini, Elena Maino, Raffaella Greco, Jacopo Peccatori, Moreno Festuccia, Francesco Zaja, Stefano Volpetti, Antonio Risitano, Renato Bassan, Paolo Corradini, Fabio Ciceri, Renato Fanin, Michele Baccarani, Alessandro Rambaldi, Francesca Bonifazi, Benedetto Bruno
Novel targeted therapies and monoclonal antibodies can be combined with allogeneic stem cell transplantation (allo-SCT) at different time-points: 1) before the transplant to reduce tumour burden, 2) as part of the conditioning in place of or in addition to conventional agents 3) after the transplant to allow long-term disease control. Areas covered This review focuses on the current integration of new drugs with allo-SCT for the treatment of major hematological malignancies for which allo-SCT has been a widely-adopted therapy...
May 16, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28505028/cytomegalovirus-disease-in-hematopoietic-stem-cell-transplant-patients-current-and-future-therapeutic-options
#11
Shigeo Fuji, Hermann Einsele, Markus Kapp
PURPOSE OF REVIEW: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has become one of the standard treatment for hematological diseases. Although the clinical outcome has improved significantly during the last decades, the morbidity and mortality after allo-HSCT are still obstacles to cure. Out of major morbidities, opportunistic virus infections such as cytomegalovirus (CMV) infection are important complications, in particular in patients who received human leukocyte antigen-mismatched HSCT...
May 12, 2017: Current Opinion in Infectious Diseases
https://www.readbyqxmd.com/read/28504201/cilia-the-sensory-antennae-in-the-eye
#12
REVIEW
Helen May-Simera, Kerstin Nagel-Wolfrum, Uwe Wolfrum
Cilia are hair-like projections found on almost all cells in the human body. Originally believed to function merely in motility, the function of solitary non-motile (primary) cilia was long overlooked. Recent research has demonstrated that primary cilia function as signalling hubs that sense environmental cues and are pivotal for organ development and function, tissue hoemoestasis, and maintenance of human health. Cilia share a common anatomy and their diverse functional features are achieved by evolutionarily conserved functional modules, organized into sub-compartments...
May 11, 2017: Progress in Retinal and Eye Research
https://www.readbyqxmd.com/read/28503959/emerging-drugs-for-prevention-of-t-cell-mediated-rejection-in-liver-and-kidney-transplantation
#13
Tiffany Cl Wong, Chung-Mau Lo, James Yy Fung
Acute and chronic graft rejection continues to be an important problem after solid organ transplantation. With the introduction of potent immunosuppressive agents such as calcineurin inhibitors, the risk of rejection has been significantly reduced. However, the adverse effects of life-long immunosuppression remain a concern, and there exist a fine balance between over-immunosuppression and risk of rejection. Areas covered. In this review, the current standard of care in immunosuppressive therapy, including the use of steroids, calcineurin inhibitors, mycophenolate prodrugs and mammalian target of rapamycin inhibitors, will be discussed...
May 15, 2017: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/28502706/reprogramming-of-central-carbon-metabolism-in-cancer-stem-cells
#14
REVIEW
Tin Lok Wong, Noélia Che, Stephanie Ma
Cancer metabolism has been studied for years and adopted in the clinic for monitoring disease progression and therapy response. Despite our growing knowledge of a distinctly altered metabolic behavior in cancer, drugs targeting cancer metabolism has remained less than promising. Recent efforts in cancer stem cell (CSC) biology suggest that a subpopulation of tumor-initiating cells within the tumor bulk to represent the root of tumor recurrence and therapy resistance. In recent years, metabolic phenotype of CSCs of various tumor types has been identified...
May 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28502128/belatacept-resistant-rejection-is-associated-with-cd28-memory-cd8-t-cells
#15
D V Mathews, W C Wakwe, S C Kim, M C Lowe, C Breeden, M E Roberts, A B Farris, E A Strobert, J B Jenkins, C P Larsen, M L Ford, R Townsend, A B Adams
Recently newer therapies have been designed to more specifically target rejection in an effort to improve efficacy and limit unwanted toxicity. Belatacept, a CD28-CD80/86 specific reagent is associated with superior patient survival and graft function than traditional therapy but its adoption as a mainstay immunosuppressive therapy has been tempered by increased rejection rates. It is essential that the underlying mechanisms associated with this rejection be elucidated before belatacept is more widely employed...
May 14, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28500691/an-interventional-study-using-cell-mediated-immunity-to-personalize-therapy-for-cytomegalovirus-infection-after-transplantation
#16
Deepali Kumar, Muhtashim Mian, Lianne Singer, Atul Humar
Cell mediated immune responses predict clinical CMV events but have not been adopted into routine practice due to lack of interventional studies. Our objective was to demonstrate the safety and feasibility of early discontinuation of antivirals based on the real-time measurement of CMV-specific CMI in patients with CMV viremia. Transplant patients were enrolled at the onset of CMV viremia requiring antiviral therapy. CD8 T-cell responses were determined using the Quantiferon-CMV assay, and results were used to guide subsequent management...
May 13, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28497159/current-status-of-chimeric-antigen-receptor-engineered-t-cell-based-and-immune-checkpoint-blockade-based-cancer-immunotherapies
#17
REVIEW
Upendra P Hegde, Bijay Mukherji
Adoptive cell therapies with chimeric antigen receptor (CAR) engineered T cells (CAR-T) and immune checkpoint inhibition (ICI)-based cancer immunotherapies have lately shown remarkable success in certain tumor types. CAR-T cell-based therapies targeting CD19 can now induce durable remissions as well as prolong disease-free survival of patients with CD19 positive treatment refractory B cell malignancies and ICI-based therapies with humanized monoclonal antibodies against the T cell inhibitory receptors CTLA-4 and PD-1 as well as against the PD-1 ligand, PD-L1, can now achieve durable remissions as well as prolongation of life of a sizeable fraction of patients with melanoma and Hodgkin's lymphoma and non-small cell cancers...
May 11, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28494274/personalized-t-cell-mediated-cancer-immunotherapy-progress-and-challenges
#18
REVIEW
Michael T Bethune, Alok V Joglekar
Immunotherapies are yielding effective treatments for several previously untreatable cancers. Until recently, vaccines and adoptive cell therapies have been designed to target public tumor antigens common to multiple patients rather than private antigens specific to a single patient. Due to the difficulty of identifying public antigens that are expressed exclusively on tumor cells, these studies have yielded both clinical successes and serious immune-related adverse events. Multiple avenues of research now underscore the centrality of tumor-specific mutated private antigens to endogenous anti-tumor immunity...
May 8, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28491035/proteomic-analysis-reveals-autophagy-as-pro-survival-pathway-elicited-by-long-term-exposure-with-5-azacitidine-in-high-risk-myelodysplasia
#19
Alessandra Romano, Cesarina Giallongo, Piera La Cava, Nunziatina L Parrinello, Antonella Chiechi, Calogero Vetro, Daniele Tibullo, Francesco Di Raimondo, Lance A Liotta, Virginia Espina, Giuseppe A Palumbo
Azacytidine (5-AZA) is the standard first-choice treatment for high-risk myelodysplasia (MDS) patients. However, the clinical outcome for those patients who interrupt treatment or whose disease failed to respond is very poor. In order to identify the cellular pathways that are modified by long-term exposure to 5-AZA, we evaluated key proteins associated with the autophagy pathway by reverse-phase microarray (RPPA). Comparing bone marrow mononucleated cells (BMMCs) obtained from 20 newly-diagnosed patients and after four 5-AZA cycles we found an increased autophagy signaling...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28490814/matrix-elasticity-modified-scaffold-loaded-with-sdf-1%C3%AE-improves-the-in-situ-regeneration-of-segmental-bone-defect-in-rabbit-radius
#20
Guobao Chen, Yonggang Lv
The effectiveness of stem-cell based therapy has been hampered by the limited availability of stem cell sources, immune rejection, and difficulties in clinical adoption and regulatory approval. These obstacles can be partially circumvented by using in situ tissue engineering that recruits the endogenous stem/progenitor cells and provides cues to direct stem cell phenotype. Here, decellularized bone scaffold is mechanically modified by coating of collagen (Col)/hydroxyapatite (HA) mixture with optimal ratio and loaded with chemokine stromal cell-derived factor-1α (SDF-1α), in which endogenous stem cell recruitment can be improved by chemokine and stem cell fate can be regulated by matrix elasticity of the scaffold...
May 10, 2017: Scientific Reports
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