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allogeneic immune therapy

E A Komech, I V Zvyagin, M V Pogorelyy, I Z Mamedov, D A Fedorenko, Y B Lebedev
Autologous hematopoietic stem cell transplantation (HSCT), a safer type of HSCT than allogeneic HSCT, is a promising therapy for patients with severe autoimmune diseases (ADs). Despite the long history of medical practice, structural changes in the adaptive immune system as a result of autologous HSCT in patients with various types of ADs remain poorly understood. In this study, we used high-throughput sequencing to investigate the structural changes in the peripheral blood T-cell repertoire in adult patients with ankylosing spondylitis (AS) during two years after autologous HSCT...
April 2018: Acta Naturae
Giselle M A Dutcher, Mehmet Asim Bilen
The field of genitourinary malignancies has been a showcase for therapeutic cancer vaccine success since the application of intravesicular Bacillus Calmette-Guerin (BCG) for bladder cancer in the 1970s and enjoyed a renaissance in 2010 with the US Food and Drug Administration (FDA) approval of sipuleucel-T for prostate cancer. Several vaccine strategies have emerged, such as autologous or allogeneic whole-tumor vaccines, DNA vaccines, use of viral vectors, and peptides as immunostimulatory adjuvants. Despite impressive early trials, vaccine monotherapy has achieved limited success in the clinical world; however, combinations of vaccine and immune checkpoint inhibition or vaccine and cytokine stimulation are expected to move the field forward...
August 12, 2018: Vaccines
Abel Trujillo-Ocampo, Hyun-Woo Cho, Amanda C Herrmann, Wilfredo Ruiz-Vazquez, Andrew B Thornton, Hong He, Dan Li, Mariam A Qazilbash, Qing Ma, Steven A Porcelli, Elizabeth J Shpall, Jeffrey Molldrem, Jin S Im
BACKGROUND AIMS: CD1d-restricted invariant natural killer (iNK) T cells are rare regulatory T cells that may contribute to the immune-regulation in allogeneic stem cell transplantation (ASCT). Here, we sought to develop an effective strategy to expand human iNK T cells for use in cell therapy to prevent graft-versus-host disease (GVHD) in ASCT. METHODS: Human iNK T cells were first enriched from peripheral blood mononuclear cells (PBMCs) using magnetic-activated cell sorting separation, then co-cultured with dendritic cells in the presence of agonist glycolipids, alpha-galactosylceramide, for 2 weeks...
July 31, 2018: Cytotherapy
Mohamed E M Saeed, Rolf Mertens, Rupert Handgretinger, Thomas Efferth
Nasopharyngeal carcinoma (NPC) is a rare disease in children with good prognosis and high cure rate. Nevertheless, certain patients have an unfavorable prognosis due to development of refractory NPC that is unresponsive to any therapeutic strategies. The current study studies a case of a 17 years-old female with non-keratinizing NPC type IIb (T2N0M0), who passed away as a consequence of resistance to chemo-, radio- and β-interferon therapy, and to an allogenic stem cell transplantation. In order to identify factors that lead to treatment failure and fatal outcome, immunohistochemical analyses of different tumor biomarkers and hierarchical cluster analysis were performed and compared with those of eight other patients with NPC who experienced complete remission following conventional therapy...
October 2018: International Journal of Oncology
Álvaro Morales-Molina, Stefano Gambera, Teresa Cejalvo, Rafael Moreno, Miguel Ángel Rodríguez-Milla, Ana Judith Perisé-Barrios, Javier García-Castro
Oncolytic virotherapy uses oncolytic viruses that selectively replicate in cancer cells. The use of cellular vehicles with migration ability to tumors has been considered to increase their delivery to target sites. Following this approach, the antitumor efficacy of the treatment Celyvir (mesenchymal stem cells infected with the oncolytic adenovirus ICOVIR-5) has been demonstrated in patients with neuroblastoma. However, the better efficacy of syngeneic or allogeneic mesenchymal stem cells as cell carriers and the specific role of the immune system in this therapy are still unknown...
July 31, 2018: Cancer Immunology, Immunotherapy: CII
SangMin Kim, Yong-Seok Han, Jun Hee Lee, Sang Hun Lee
Mesenchymal stem cells (MSCs) are widely used in transplantation therapy due to their multilineage differentiation potential, abundance, and immuno-modulating ability. However, the risk of allograft rejection limits their application. Here, we proposed a novel method to facilitate MSC transplantation with enhanced applicability and efficacy. We cultured human adipose-derived MSCs in a 3D culture under in vitro expansion conditions and under conventional 2D adherent culture conditions. MSC spheroids promoted extracellular matrix molecules that stimulate MSC proliferation, and produced more angiogenic cytokines such as vascular endothelial growth factor, hepatocyte growth factor, and fibroblast growth factor than 2D-cultured MSCs...
August 2018: Tissue & Cell
Arjan A van de Loosdrecht, Sandra van Wetering, Saskia J A M Santegoets, Satwinder Kaur Singh, Corien M Eeltink, Yvonne den Hartog, Malika Koppes, Jorn Kaspers, Gert J Ossenkoppele, Ada M Kruisbeek, Tanja D de Gruijl
In elderly acute myeloid leukemia (AML) patients post-remission treatment options are associated with high comorbidity rates and poor survival. Dendritic cell (DC)-based immunotherapy is a promising alternative treatment strategy. A novel allogeneic DC vaccine, DCP-001, was developed from an AML-derived cell line that uniquely combines the positive features of allogeneic DC vaccines and expression of multi-leukemia-associated antigens. Here, we present data from a phase I study conducted with DCP-001 in 12 advanced-stage elderly AML patients...
July 23, 2018: Cancer Immunology, Immunotherapy: CII
Paloma Riquelme, Jan Haarer, Anja Kammler, Lisa Walter, Stefan Tomiuk, Norbert Ahrens, Anja K Wege, Ivan Goecze, Daniel Zecher, Bernhard Banas, Rainer Spang, Fred Fändrich, Manfred B Lutz, Birgit Sawitzki, Hans J Schlitt, Jordi Ochando, Edward K Geissler, James A Hutchinson
Human regulatory macrophages (Mreg) have shown early clinical promise as a cell-based adjunct immunosuppressive therapy in solid organ transplantation. It is hypothesised that recipient CD4+ T cell responses are actively regulated through direct allorecognition of donor-derived Mregs. Here we show that human Mregs convert allogeneic CD4+ T cells to IL-10-producing, TIGIT+ FoxP3+ -induced regulatory T cells that non-specifically suppress bystander T cells and inhibit dendritic cell maturation. Differentiation of Mreg-induced Tregs relies on multiple non-redundant mechanisms that are not exclusive to interaction of Mregs and T cells, including signals mediated by indoleamine 2,3-dioxygenase, TGF-β, retinoic acid, Notch and progestagen-associated endometrial protein...
July 20, 2018: Nature Communications
Jian-Ping Zhang, Rui Zhang, Shih-Ting Tsao, Yu-Chen Liu, Xiaochuan Chen, Dao-Pei Lu, Paul Castillo, Lung-Ji Chang
No abstract text is available yet for this article.
July 24, 2018: Blood Advances
Handan Sevim, Yusuf Çetin Kocaefe, Mehmet Ali Onur, Duygu Uçkan-Çetinkaya, Özer Aylin Gürpınar
BACKGROUND: Familial hemophagocytic lymphohistiocytosis 2 (FHL2) is the most common familial type of hemophagocytic lymphohistiocytosis with immune dysregulation. FHL2 patients have mutations in the perforin gene which cause overactivation and proliferation of cytotoxic T lymphocytes and natural killer cells. Perforin is the key component of the cytolytic granule response function of cytotoxic T lymphocytes and natural killer cells. Perforin dysfunction causes a cytotoxic immune deficiency with a clinical outcome of uncontrolled and continuous immune stimulation response...
July 18, 2018: Stem Cell Research & Therapy
Mara Bonardi, Elena Turpini, Giuseppina Sanfilippo, Tommaso Mina, Alessandra Tolva, Federico Zappoli Thyrion
Hematopoietic stem cell transplantation (HSCT) is the only therapy for a subset of patients with malignant and nonmalignant diseases. Central nervous system (CNS) complications continue to be an important cause of morbidity and significantly contribute to mortality after HSCT. These complications include infections, cerebrovascular lesions, therapy-induced diseases, metabolic disturbances, and post-HSCT carcinogenesis. Following HSCT, three phases can be identified on the basis of the patient's immune status: the pre-engraftment period (<30 days after HSCT), the early postengraftment period (30-100 days after HSCT), and the late postengraftment period (>100 days after HSCT)...
July 2018: Radiographics: a Review Publication of the Radiological Society of North America, Inc
Diego Adrianzen Herrera, Sabarish Ayyappan, Sakshi Jasra, Noah Kornblum, Olga Derman, Aditi Shastri, Ioannis Mantzaris, Amit Verma, Ira Braunschweig, Murali Janakiram
Progressive multifocal leukoencephalopathy (PML) is a life-threatening opportunistic infection of immunomodulatory therapies. PML cases reported in PubMed (1995-2017) following stem-cell transplantation (HSCT) or chemoimmunotherapy (CIT) for hematologic malignancies were reviewed. We found 107 cases, 40% were HSCT recipients (32 allogeneic, 11 autologous) and 40% indolent lymphomas receiving monoclonal antibodies (mAbs). HSCT cases had longer time to PML diagnosis (10.8 vs. 4 months, p < .001), higher proportion of PML therapy response (58% vs...
July 3, 2018: Leukemia & Lymphoma
J K Chai, Q Y Zheng, L G Li, S J Ye, Z G Wen, J J Li, S J Wang, D J Li, W Z Xie, J L Wang, H L Hai, R J Chen, J C Shao, H Wang, Q Li, Z M Xu, L P Xu, H J Xiao, L M Zhou, R Feng
Objective: To summarize the measures and experience of treatment in mass extremely severe burn patients. Methods: The clinical data and treatment of 8 extremely severe burn patients in August 2 Kunshan factory aluminum dust explosion accident who were admitted in the 100th Hospital of PLA on August 2nd, 2014, were retrospectively analyzed. There were 4 males and 4 females, aging 22-45 (34±7) years, with total burn area of 55%-98% [(89±15)%] total body surface area (TBSA) and full-thickness burn area of 45%-97% [(80±21)%] TBSA...
June 20, 2018: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
Adam J Lamble, Evan F Lind
Immunotherapies, such as chimeric antigen receptor T cells, bispecific antibodies, and immune checkpoint inhibitors, have emerged as promising modalities in multiple hematologic malignancies. Despite the excitement surrounding immunotherapy, it is currently not possible to predict which patients will respond. Within solid tumors, the status of the immune microenvironment provides valuable insight regarding potential responses to immune therapies. Much less is known about the immune microenvironment within hematologic malignancies but the characteristics of this environment are likely to serve a similar predictive role...
2018: Frontiers in Oncology
Lidia Garcia-Bonilla, David Brea, Corinne Benakis, Diane A Lane, Michelle Murphy, Jamie Moore, Gianfranco Racchumi, Xinran Jiang, Costantino Iadecola, Josef Anrather
Exposure to low-dose lipopolysaccharide (LPS) before cerebral ischemia is neuroprotective in stroke models, a phenomenon termed preconditioning (PC). Although it is well established that LPS-PC induces central and peripheral immune responses, the cellular mechanisms modulating ischemic injury remain unclear. Here, we investigated the role of immune cells in the brain protection afforded by PC and tested whether monocytes may be reprogrammed by ex vivo LPS exposure, thus modulating inflammatory injury after cerebral ischemia in male mice...
July 25, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Alessandro Isidori, Federica Loscocco, Marilena Ciciarello, Giulia Corradi, Mariangela Lecciso, Darina Ocadlikova, Sarah Parisi, Valentina Salvestrini, Sergio Amadori, Giuseppe Visani, Antonio Curti
Acute myeloid leukemia (AML) is a disease, which mainly affects the elderly population. Unfortunately, the prognosis of patients aged >65 years is dismal, with 1-year overall survival approaching 10% with conventional therapies. The hypothesis of harnessing the immune system against cancer, including leukemia, has been postulated for a long time, and several clinical attempts have been made in this field. In the last years, we increased our knowledge about the interplay between AML and immune cells, but no major improvement has been translated, up to now, from bench to bedside...
June 22, 2018: Cancers
Alexis Leonard, John F Tisdale
Sickle cell disease (SCD) is the most common inherited hemoglobinopathy worldwide, and is a life-limiting disease with limited therapeutic options to reduce disease severity. Despite being a monogenic disorder, the clinical phenotypes of SCD are variable, with few reliable predictors of disease severity easily identifying patients where the benefits of curative therapy outweigh the risks. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative option, though significant advances in gene therapy raise the promise for additional curative methods...
July 2018: Expert Review of Hematology
Koji Kato
Over the past few decades, the advancements in the area of molecular-targeted therapy have revolutionized the treatment of hematological malignancies, thereby altering the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, allo-HSCT continues to play an essential role in the treatment of hematological malignancies because the cure is rare by targeted therapy alone. In the modern era, the incorporation of molecular-targeted therapy, including chemotherapy and allo-HSCT, into the conventional therapy is the key to attaining therapeutic success...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Maaike V J Braham, Monique C Minnema, Tineke Aarts, Zsolt Sebestyen, Trudy Straetemans, Anna Vyborova, Jurgen Kuball, F Cumhur Öner, Catherine Robin, Jacqueline Alblas
Bone marrow niches support multiple myeloma, providing signals and cell-cell interactions essential for disease progression. A 3D bone marrow niche model was developed, in which supportive multipotent mesenchymal stromal cells and their osteogenic derivatives were co-cultured with endothelial progenitor cells. These co-cultured cells formed networks within the 3D culture, facilitating the survival and proliferation of primary CD138+ myeloma cells for up to 28 days. During this culture, no genetic drift was observed within the genomic profile of the primary myeloma cells, indicating a stable outgrowth of the cultured CD138+ population...
2018: Oncoimmunology
Jeffrey M H Liu, Xiaomin Zhang, Shelby Joe, Xunrong Luo, Lonnie D Shea
Introduction: The development of novel immunomodulatory strategies that might decrease the need for systemic immune suppression would greatly enable the utility of cell-based therapies. Cell transplantation on biomaterial scaffolds offers a unique opportunity to engineer a site to locally polarize immunogenic antigen generation. Herein, we investigated the localized delivery of IL-33, which is a novel cytokine that has been shown to have beneficial immunomodulatory effects in certain transplant models as mediating anti-inflammatory properties in the adipose tissue, to determine its feasibility for use as an immunomodulatory agent...
March 2018: Journal of immunology and regenerative medicine
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