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Cellular Immunotherapy

Xueyan Zhang, Fengbo Wu, Ke Men, Rong Huang, Bailin Zhou, Rui Zhang, Rui Zou, Li Yang
As a novel toll-like receptor 9 (TLR9) agonist, synthetic unmethylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotides can stimulate a Th1 immune response and potentially be used as therapeutic agents or vaccine adjuvants for the treatment of cancer. However, some drawbacks of CpG limit their applications, such as rapid elimination by nuclease-mediated degradation and poor cellular uptake. Therefore, repeat high-dose drug administration is required for treatment. In this work, a CpG delivery system based on 3-aminopropyltriethoxysilane (APTES)-modified Fe3 O4 nanoparticles (FeNPs) was designed and studied for the first time to achieve better bioactivity of CpG...
August 17, 2018: Nanoscale Research Letters
Andrea Zhe Ern Lee, Louise Soo Yee Tan, Chwee Ming Lim
Undifferentiated Nasopharyngeal carcinoma (NPC) is ubiquitously identified with the Epstein-Barr virus (EBV), making this cancer a suitable candidate for cellular-based immunotherapy (CBI) due to its expression of potentially targetable tumor-associated viral antigens. Various preclinical and clinical studies have explored the use of cytotoxic T cells (CTLs), tumor-infiltrating lymphocytes (TILs), natural killer (NK) cells, and dendritic cells (DCs) in the treatment of both refractory and locally advanced NPC with some success...
September 2018: Oral Oncology
Jing Shi, Tian-Tian Ma, Hua-Sheng Liu
In recent years, with the incidence of malignant tumors increasing year by year, its treatment has been made great progress on the basis of traditional treatments such as surgery, radiotherapy and chemotherapy, it mainly focuses on rapid development of cellular immunotherapy. The efficacy of dendritic cells combined with cytokine induced killer cell (DC-CIK) immunotherapy for cancer patients is positive, it shows good antitumor activities and the abilities to reconstruct and enhance the immune system of tumor patients in clinical application, it has potential application value...
August 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Fu-Sheng Gao, Yu-Tao Zhan, Xu-Dong Wang, Chuan Zhang
AIM: DNA vaccines have emerged as a promising strategy for cancer immunotherapy; however, their immunogenicity is weak. Fms-like tyrosine kinase 3-ligand (Flt3L) has been exploited for its ability to increase the proliferation of dendritic cells (DCs). The aim of the present study was to investigate whether co-administration of an adjuvant plasmid expressing mouse Flt3L and a DNA vaccine of the Mucin 1 (MUC1) antigen enhances immune responses. METHODS: The recombinant plasmids pVAX1-MUC1 and pVAX1-Flt3L were constructed and injected into mice intramuscularly (i...
August 15, 2018: Immunopharmacology and Immunotoxicology
Cameron McDonald-Hyman, James T Muller, Michael Loschi, Govindarajan Thangavelu, Asim Saha, Sudha Kumari, Dawn K Reichenbach, Michelle J Smith, Guoan Zhang, Brent H Koehn, Jiqiang Lin, Jason S Mitchell, Brian T Fife, Angela Panoskaltsis-Mortari, Colby J Feser, Andrew Kemal Kirchmeier, Mark J Osborn, Keli L Hippen, Ameeta Kelekar, Jonathan S Serody, Laurence A Turka, David H Munn, Hongbo Chi, Thomas A Neubert, Michael L Dustin, Bruce R Blazar
Regulatory T-cells (Treg) are critical for maintaining immune homeostasis. However, current Treg immunotherapies do not optimally treat inflammatory diseases in patients. Understanding the cellular processes that control Treg function may allow for the augmentation of therapeutic efficacy. In contrast to activated conventional T-cells, where protein kinase C-θ (PKC-θ) localizes to the contact-point between T-cells and antigen-presenting cells, in human and mouse Treg, PKC-θ localizes to the opposite end of the cell in the distal pole complex (DPC)...
August 14, 2018: Journal of Clinical Investigation
Deepika Kumar, Mina L Xu
Lymphoma microenvironment is a complex system composed of stromal cells, blood vessels, immune cells as well as extracellular matrix, cytokines, exosomes, and chemokines. In this review, we describe the function, localization, and interactions between various cellular components. We also summarize their contribution to lymphoma immunity in the era of immunotherapy. Publications were identified from searching Pubmed. Primary literature was carefully evaluated for replicability before incorporating into the review...
2018: Frontiers in Oncology
Zili Gu, Qingjie Wang, Yanbin Shi, Yi Huang, Jing Zhang, Xinke Zhang, Guimei Lin
Immunotherapy has exhibited enormous practice in the treatment of melanoma because of the intrinsic properties of tumor. Tumor can downmodulate immune function via multiple mechanisms such as immune checkpoint pathways. The PD-L1 monoclonal antibodies that block the PD1/PD-L1 pathway, which induced tumor cells to evade an immune attack, can delay tumor growth efficiently with inevitable disadvantages such as low selectivity and systemic toxicity. Nanomedicine is clearly an approach that holds tremendous potential for addressing the shortcomings and assisting delivery of drugs with proper biodistribution...
August 7, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Kai Jun Koh, Yi Liu, Seng Han Lim, Xian Jun Loh, Lifeng Kang, Chee Yen Lim, Kyle K L Phua
In this paper, we report a proof of concept study on the fabrication, characterization and therapeutic evaluation of in vitro transcribed messenger RNA (mRNA) loaded in a dissolving microneedle patch (RNApatch). We show that low molecular weight polyvinylpyrrolidone (PVP) can directly be used without further purification for RNApatch fabrication with no detectable mRNA degradation. Physical and functional integrity of mRNA stored within the RNApatch are completely preserved for at least 2 weeks under ambient conditions...
August 7, 2018: Scientific Reports
Kris M Mahadeo, Sajad J Khazal, Hisham Abdel-Azim, Julie C Fitzgerald, Agne Taraseviciute, Catherine M Bollard, Priti Tewari, Christine Duncan, Chani Traube, David McCall, Marie E Steiner, Ira M Cheifetz, Leslie E Lehmann, Rodrigo Mejia, John M Slopis, Rajinder Bajwa, Partow Kebriaei, Paul L Martin, Jerelyn Moffet, Jennifer McArthur, Demetrios Petropoulos, Joan O'Hanlon Curry, Sarah Featherston, Jessica Foglesong, Basirat Shoberu, Alison Gulbis, Maria E Mireles, Lisa Hafemeister, Cathy Nguyen, Neena Kapoor, Katayoun Rezvani, Sattva S Neelapu, Elizabeth J Shpall
In 2017, an autologous chimeric antigen receptor (CAR) T cell therapy indicated for children and young adults with relapsed and/or refractory CD19+ acute lymphoblastic leukaemia became the first gene therapy to be approved in the USA. This innovative form of cellular immunotherapy has been associated with remarkable response rates but is also associated with unique and often severe toxicities, which can lead to rapid cardiorespiratory and/or neurological deterioration. Multidisciplinary medical vigilance and the requisite health-care infrastructure are imperative to ensuring optimal patient outcomes, especially as these therapies transition from research protocols to standard care...
August 6, 2018: Nature Reviews. Clinical Oncology
Shimaa Ibrahim Abdelmenym Mohamed, Ibrahim Jantan, Mohd Azlan Nafiah, Mohamed Ali Seyed, Kok Meng Chan
BACKGROUND: Dendritic cells (DCs) are unique antigen presenting cells (APC) which play a pivotal role in immunotherapy and induction of an effective immune response against tumors. In the present study, 80% ethanol extract of Phyllanthus amarus was used to generate tumor lysate (TLY) derived from HCT 116 and MCF-7 cancer cell lines via induction of apoptosis. Monocyte-derived DCs were generated ex vivo from the adherent population of peripheral blood mononuclear cells (PBMCs). The generated TLY were used to impulse DCs to investigate its effect on their cellular immune functions including antigen presentation capacity, phagocytic activity, chemotaxis capacity, T-cell proliferation and cytokines release...
August 6, 2018: BMC Complementary and Alternative Medicine
Kathleen W Phelan, Anjali S Advani
PURPOSE OF REVIEW: Treatment options for patients with acute lymphoblastic leukemia (ALL) beyond standard chemotherapy have grown significantly in recent years. In this review, we highlight new targeted therapies in ALL, with an emphasis on immunotherapy. RECENT FINDINGS: Major advances include antibody-based therapies, such as naked monoclonal antibodies, antibody-drug conjugates and bispecific T cell engaging (BiTE) antibodies, as well as adoptive cellular therapies such as chimeric antigen receptor (CAR) T cells...
August 4, 2018: Current Hematologic Malignancy Reports
Yi Shu, Chao Yang, Xiaojuan Ji, Linghuan Zhang, Yang Bi, Ke Yang, Mengjia Gong, Xing Liu, Qi Guo, Yuxi Su, Xiangyang Qu, Guoxin Nan, Chen Zhao, Zongyue Zeng, Xinyi Yu, Ruyi Zhang, Shujuan Yan, Jiayan Lei, Ke Wu, Ying Wu, Liping An, Shifeng Huang, Cheng Gong, Chengfu Yuan, Wei Liu, Bo Huang, Yixiao Feng, Bo Zhang, Zhengyu Dai, Yi Shen, Wenping Luo, Xi Wang, Rex C Haydon, Hue H Luu, Russell R Reid, Jennifer Moriatis Wolf, Michael J Lee, Tong-Chuan He, Yasha Li
Human mesenchymal stem cells (MSCs) are a heterogeneous subset of nonhematopoietic multipotent stromal stem cells and can differentiate into mesodermal lineage, such as adipocytes, osteocytes, and chondrocytes, as well as ectodermal and endodermal lineages. Human umbilical cord (UC) is one of the most promising sources of MSCs. However, the molecular and cellular characteristics of UC-derived MSCs (UC-MSCs) require extensive investigations, which are hampered by the limited lifespan and the diminished potency over passages...
August 4, 2018: Journal of Cellular Biochemistry
Ping Xu, Yu Pang, Junchi Xu, Hui Chen, Peijun Tang, Meiying Wu
In this report, we identified a multidrug-resistant tuberculosis (MDR-TB) patient who remained acid-fast bacilli culture positive despite aggressive WHO-directed therapy. Between July 2014 and February 2015, she received eight courses of cytokine-induced killer (CIK) cell-based adoptive cellular immunotherapy in combination to the second-line anti-TB treatment. This case achieved culture conversion, and experienced no relapse during 2-year follow-up under the treatment with CIK cell-based adoptive cellular immunotherapy...
August 2018: Immunotherapy
Charlotte Graham, Rebecca Hewitson, Antonio Pagliuca, Reuben Benjamin
Cellular therapy is a key tool to treat haematological malignancies. Over 40,000 allogeneic and autologous haematopoietic stem cell transplants (HSCTs) are performed annually across Europe.1 Since 2017, a new T cell therapy, chimeric antigen receptor-T (CAR-T) cells have been licensed outside clinical trials. CAR-T cells have extremely potent antitumour activity, but also have a profile of toxic side effects not seen before. Cytokine release syndrome (CRS) and CAR-T cell-related encephalopathy syndrome (CRES) are common, predictable and potentially lethal side effects...
August 2018: Clinical Medicine: Journal of the Royal College of Physicians of London
Catherine Bollard
No abstract text is available yet for this article.
June 2018: Clinical Advances in Hematology & Oncology: H&O
Mariona Pascal, Marina Perez-Gordo, Teresa Caballero, Maria M Escribese, M Natividad Lopez Longo, Olga Luengo, Luis Manso, Victor Matheu, Elena Seoane, Miguel Zamorano, Moisés Labrador, Cristobalina Mayorga
Allergic diseases, such as respiratory, cutaneous, and food allergy, have dramatically increased in prevalence over the last few decades. Recent research points to a central role of the microbiome, which is highly influenced by multiple environmental and dietary factors. It is well established that the microbiome can modulate the immune response, from cellular development to organ and tissue formation exerting its effects through multiple interactions with both the innate and acquired branches of the immune system...
2018: Frontiers in Immunology
Mengming Hu, Jun Zhang, Junting Yang, Yue Cao, Jinshun Qi
Immunotherapy for Alzheimer's disease (AD) remains promising in the improvement of cognition and memory via the clearing of amyloid-β protein (Aβ) in the AD brain, despite some side effects. Our previous studies demonstrated that the 31-35 sequence of the Aβ molecule was the shortest active center and that polyclonal anti-Aβ31-35 antibody reduced neuronal apoptosis and cognitive impairments induced with acute Aβ application. The present study designed a novel single-chain variable fragment (scFv) monoclonal anti-Aβ31-35 antibody (scFv17) that specifically recognized extracellular Aβ and observed protective effects of scFv17 on pathological impairments in APP/PS1 transgenic mice...
July 31, 2018: Journal of Molecular Neuroscience: MN
Rose Nganga, Natalia Oleinik, Besim Ogretmen
Mechanistic details for the roles of sphingolipids and their downstream targets in the regulation of tumor growth, response to chemo/radiotherapy, and metastasis have been investigated in recent studies using innovative molecular, genetic and pharmacologic tools in various cancer models. Induction of ceramide generation in response to cellular stress by chemotherapy, radiation, or exogenous ceramide analog drugs mediates cell death via apoptosis, necroptosis, or mitophagy. In this chapter, distinct functions and mechanisms of action of endogenous ceramides with different fatty acyl chain lengths in the regulation of cancer cell death versus survival will be discussed...
2018: Advances in Cancer Research
Jannie Borst, Tomasz Ahrends, Nikolina Bąbała, Cornelis J M Melief, Wolfgang Kastenmüller
Cancer immunotherapy aims to promote the activity of cytotoxic T lymphocytes (CTLs) within a tumour, assist the priming of tumour-specific CTLs in lymphoid organs and establish efficient and durable antitumour immunity. During priming, help signals are relayed from CD4+ T cells to CD8+ T cells by specific dendritic cells to optimize the magnitude and quality of the CTL response. In this Review, we highlight the cellular dynamics and membrane receptors that mediate CD4+ T cell help and the molecular mechanisms of the enhanced antitumour activity of CTLs...
July 29, 2018: Nature Reviews. Immunology
Aussara Panya, Chutamas Thepmalee, Nunghathai Sawasdee, Jatuporn Sujjitjoon, Nattaporn Phanthaphol, Mutita Junking, Sopit Wongkham, Pa-Thai Yenchitsomanus
Cholangiocarcinoma (CCA) is a cancer of the bile ducts that is associated with poor prognosis and poor treatment outcome. Approximately one-third of CCA patients can undergo surgery, but the recurrence rate is high and chemotherapy often cannot satisfactorily prolong survival. Cellular immunotherapy based on adoptive T-cell transfer is a potential treatment for CCA; however, the development of this technology and the search for an appropriate tumor-associated antigen are still ongoing. To enhance the cytotoxic activity of effector T cells against CCA, we developed self-differentiated monocyte-derived dendritic cells (SD-DC) presenting cAMP-dependent protein kinase type I-alpha regulatory subunit (PRKAR1A), which is an overexpressed protein that plays a role in the regulation of tumor growth to activate T cells for CCA cell killing...
July 28, 2018: Cancer Immunology, Immunotherapy: CII
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