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allogeneic immune therapy

Rafael Moreno, Carlos Alberto Fajardo, Marti Farrera-Sal, Ana Judith Perisé-Barrios, Álvaro Morales-Molina, Ahmed Abdullah Al-Zaher, Javier Garcia-Castro, Ramon Alemany
Several studies have evaluated the efficacy of using human oncolytic adenovirus-loaded mesenchymal stem cells for cancer treatment. For example, we have described the antitumor efficacy of CELYVIR, autologous bone marrow mesenchymal stem cells infected with the oncolytic adenovirus ICOVIR-5, for treatment of neuroblastoma patients. Results from this clinical trial point out the role of the immune system in the clinical outcome. In this context, a better understanding of the immunophenotypic changes of human mesenchymal stem cells upon adenoviral infection and how these changes affect human autologous or allogeneic peripheral blood mononuclear cells (PBMCs) could guide strategies to improve the antitumor efficacy of infected Mesenchymal Stem Cells (MSCs)...
October 15, 2018: Molecular Cancer Therapeutics
Marta González-Vicent, Miguel A Díaz Perez
PURPOSE OF REVIEW: Nowadays, T-cell-depleted haploidentical transplantation is considered a valid approach for children lacking a human leukocyte antigen (HLA) identical donor for allogeneic transplantation. This kind of allogeneic transplant is now widely used especially for pediatric patients with high-risk hematological malignancies. However, relapsing disease and life-threatening viral infections are still relevant clinical problems as a consequence of delayed immune reconstitution...
November 2018: Current Opinion in Oncology
Sandro Matosevic
Natural killer (NK) cells are powerful immune effectors whose antitumor activity is regulated through a sophisticated network of activating and inhibitory receptors. As effectors of cancer immunotherapy, NK cells are attractive as they do not attack healthy self-tissues nor do they induce T cell-driven inflammatory cytokine storm, enabling their use as allogeneic adoptive cellular therapies. Clinical responses to adoptive NK-based immunotherapy have been thwarted, however, by the profound immunosuppression induced by the tumor microenvironment, particularly severe in the context of solid tumors...
2018: Journal of Immunology Research
Koji Kato
Recent advances in the field of molecular-targeted therapy have revolutionized the treatment of hematological malignancies. Consequentially, the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) has dramatically changed. However, allo-HSCT remains vital in the treatment of hematological malignancies because cure is rarely achieved by targeted therapy only. In the new era of molecular-targeted treatment, its incorporation into allo-HSCT is key to achieving therapeutic success. In particular, the understanding of the immune impact of molecular-targeted therapy on graft-versus-host-disease and graft-versus-leukemia is essential to improve the outcome of allo-HSCT...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Juliette Peltzer, Marc Aletti, Nadira Frescaline, Elodie Busson, Jean-Jacques Lataillade, Christophe Martinaud
Systemic Sclerosis (SSc) is a rare chronic disease, related to autoimmune connective tissue diseases such as Systemic Lupus Erythematosus and Sjögren's Syndrome. Although its clinical heterogeneity, main features of the disease are: extensive tissue fibrosis with increase matrix deposition in skin and internal organ, microvascular alterations and activation of the immune system with autoantibodies against various cellular antigens. In the diffuse cutaneous scleroderma subtype, the disease is rapidly progressive with a poor prognosis, leading to failure of almost any internal organ, especially lung which is the leading cause of death...
2018: Frontiers in Immunology
Cornelia S Link-Rachner, Anne Eugster, Elke Rücker-Braun, Falk Heidenreich, Uta Oelschlägel, Andreas Dahl, Christian Klesse, Matthias Kuhn, Jan Moritz Middeke, Martin Bornhäuser, Ezio Bonifacio, Johannes Schetelig
Alloreactivity or opportunistic infections following allogeneic stem cell transplantation are difficult to predict and contribute to post-transplantation mortality. How these immune reactions result in changes to the T cell receptor repertoire remains largely unknown. Using next generation sequencing, the T cell receptor alpha repertoire of naive and memory CD8+ T cells from 25 patients who had received different forms of allogeneic transplantation was analysed. In parallel, reconstitution of the CD8+/CD4+ T cell subsets was mapped using flow cytometry...
September 27, 2018: Haematologica
Anna Thunström Salzer, Maria J Niemiec, Ava Hosseinzadeh, Marios Stylianou, Fredrik Åström, Marc Röhm, Clas Ahlm, Anders Wahlin, David Ermert, Constantin F Urban
Neutrophils are crucial for the human innate immunity and constitute the majority of leukocytes in circulation. Thus, blood neutrophil counts serve as a measure for the immune system's functionality. Hematological patients often have low neutrophil counts due to disease or chemotherapy. To increase neutrophil counts and thereby preventing infections in high-risk patients, recombinant G-CSF is widely used as adjunct therapy to stimulate the maturation of neutrophils. In addition, G-CSF is utilized to recruit stem cells (SCs) into the peripheral blood of SC donors...
2018: Frontiers in Immunology
Tor Henrik Anderson Tvedt, Guro K Melve, Galina Tsykunova, Aymen Bushra Ahmed, Annette K Brenner, Øystein Bruserud
Interleukin-6 (IL-6) contributes to the development of immune-mediated complications after allogeneic stem cell transplantation. However, systemic IL-6 levels also increase during granulocyte colony-stimulating factor (G-CSF) mobilization of hematopoietic stem cells in healthy donors, but it is not known whether this mobilization alters systemic levels of other IL-6 family cytokines/receptors and whether such effects differ between donors. We examined how G-CSF administration influenced C-reactive protein (CRP) levels (85 donors) and serum levels of IL-6 family cytokines/receptors (20 donors)...
September 22, 2018: International Journal of Molecular Sciences
Pauline L de Goeje, Yarne Klaver, Margaretha E H Kaijen-Lambers, Anton W Langerak, Heleen Vroman, André Kunert, Cor H J Lamers, Joachim G J V Aerts, Reno Debets, Rudi W Hendriks
Introduction: Malignant pleural mesothelioma (MPM) is a malignancy with a very poor prognosis for which new treatment options are urgently needed. We have previously shown that dendritic cell (DC) immunotherapy provides a clinically feasible treatment option. In the current study, we set out to assess the immunological changes induced by DC immunotherapy in peripheral blood of MPM patients. Methods: Peripheral blood was collected from nine patients enrolled in a phase I dose escalation study, before and after treatment with DCs that were pulsed with an allogeneic tumor lysate preparation consisting of a mixture of five cultured mesothelioma cell lines...
2018: Frontiers in Immunology
Erin E Hillhouse, Stéphanie Thiant, Moutuaata M Moutuou, Félix Lombard-Vadnais, Rachel Parat, Jean-Sébastien Delisle, Imran Ahmad, Denis-Claude Roy, Martin Guimond, Jean Roy, Sylvie Lesage
Chronic graft-versus-host disease (cGVHD) is a major complication, affecting 50% to 80% of long-term survivors of allogeneic hematopoietic stem cell transplantation. Current cGVHD therapies are neither specific nor curative, and patients are typically maintained for several months to years under immunosuppressive regimens that are associated with important side effects and increased susceptibility to life-threatening infections. As a result, continued investigation into the pathology of the disease and the search for novel diagnostic and therapeutic strategies to treat cGVHD remains a high priority...
September 19, 2018: Biology of Blood and Marrow Transplantation
Supinya Iamsawat, Anusara Daenthanasanmak, Jessica Heinrichs Voss, Hung Nguyen, David Bastian, Chen Liu, Xue-Zhong Yu
CD8+ induced regulatory T cells (iTregs) have been identified to suppress alloreactive immune responses and expressed regulatory T cell (Treg) ontological markers as similar as CD4+ iTregs. However, adoptive transfer of CD8+ iTreg-based therapy is hampered by the instability of Treg specific-transcription factor, Foxp3. As CD8+ iTregs were previously demonstrated to possess superior tumor-killing ability to CD4+ iTregs, adoptive transfer of stabilized CD8+ iTregs would be a potential therapy to prevent tumor relapse during graft-versus-leukemia disease (GVHD) treatment...
September 21, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Nuri Karadurmus, Ugur Sahin, Bilgin Bahadir Basgoz, Fikret Arpaci, Taner Demirer
Breast cancer (BC) has a high mortality rate and metastatic BC is almost incurable despite hormonal therapy and chemotherapy. The second and third lines of chemotherapies usually yield transient responses and the median survival is generally as low as 18-24 months. Autologous and allogeneic hematopoietic stem cell transplantation (HSCT) have been extensively investigated in this setting. The presence of immune mediated anti-tumor effects referred to as graft-versus-tumor (GvT) effects after allogeneic HSCT among patients with solid tumors have been clearly defined...
April 1, 2018: International Journal of Hematology-oncology and Stem Cell Research
Tobias Winkler, Carsten Perka, Philipp von Roth, Alison N Agres, Henning Plage, Bernd Preininger, Matthias Pumberger, Sven Geissler, Esther Lukasiewicz Hagai, Racheli Ofir, Lena Pinzur, Eli Eyal, Gisela Stoltenburg-Didinger, Christian Meisel, Christine Consentius, Mathias Streitz, Petra Reinke, Georg N Duda, Hans-Dieter Volk
BACKGROUND: No regenerative approach has thus far been shown to be effective in skeletal muscle injuries, despite their high frequency and associated functional deficits. We sought to address surgical trauma-related muscle injuries using local intraoperative application of allogeneic placenta-derived, mesenchymal-like adherent cells (PLX-PAD), using hip arthroplasty as a standardized injury model, because of the high regenerative and immunomodulatory potency of this cell type. METHODS: Our pilot phase I/IIa study was prospective, randomized, double blind, and placebo-controlled...
September 19, 2018: Journal of Cachexia, Sarcopenia and Muscle
Ulrich Jarry, Noémie Joalland, Cynthia Chauvin, Béatrice Clemenceau, Claire Pecqueur, Emmanuel Scotet
Glioblastoma multiforme (GBM), the most frequent and aggressive primary brain cancer in adults, is generally associated with a poor prognosis, and scarce efficient therapies have been proposed over the last decade. Among the promising candidates for designing novel therapeutic strategies, cellular immunotherapies have been targeted to eliminate highly invasive and chemo-radioresistant tumor cells, likely involved in a rapid and fatal relapse of this cancer. Thus, administration(s) of allogeneic GBM-reactive immune cell effectors, such as human Vϒ9Vδ2 T lymphocytes, in the vicinity of the tumor would represents a unique opportunity to deliver efficient and highly concentrated therapeutic agents directly into the site of brain malignancies...
September 1, 2018: Journal of Visualized Experiments: JoVE
L Scobie, C Galli, P Gianello, E Cozzi, H-J Schuurman
The main benefit of xenotransplantation is its potential to overcome the worldwide organ shortage experienced in allotransplantation. Allogeneic transplantation is the only successful therapy for several life-threatening diseases, with cell, tissue or organ donation only partially meeting the demand and many patients dying while waiting for treatment. With supply falling short of demand, it is foreseen that the use of porcine material may at some stage overcome the existing gap between organ availability and clinical need...
April 2018: Revue Scientifique et Technique
Brian L K Miller, Payal Garg, Ben Bronstein, Elizabeth LaPointe, Herb Lin, David M Charytan, Arno W Tilles, Biju Parekkadan
Introduction: The pathophysiology of acute kidney injury (AKI) involves damage to renal epithelial cells, podocytes, and vascular beds that manifests into a deranged, self-perpetuating immune response and peripheral organ dysfunction. Such an injury pattern requires a multifaceted therapeutic to alter the wound healing response systemically. Mesenchymal stromal cells (MSCs) are a unique source of secreted factors that can modulate an inflammatory response to acute organ injury and enhance the repair of injured tissue at the parenchymal and endothelial levels...
September 2018: KI Reports
Donald B Kohn, Michael S Hershfield, Jennifer M Puck, Alessandro Aiuti, Annaliesse Blincoe, H Bobby Gaspar, Luigi D Notarangelo, Eyal Grunebaum
Inherited defects in adenosine deaminase (ADA) cause a subtype of severe combined immunodeficiency (SCID), known as ADA-SCID. Most affected infants can be diagnosed while still asymptomatic by a SCID newborn screening test, allowing early initiation of therapy. We reviewed the evidence currently available and propose a consensus management strategy. In addition to the treatment of the immune deficiency of ADA-SCID, patients should be followed for specific non-infectious respiratory, neurological and biochemical complications associated with ADA deficiency...
September 5, 2018: Journal of Allergy and Clinical Immunology
Jaroslav Čermák
Aplastic anemia - bone marrow failure (AA) is defined as pancytopenia with hypocellular bone marrow without signs of marrow fibrosis or of presence of abnormal cells. Recent studies showed that most of AA cases might be mediated by immune mechanisms. Toxic agent leads to expression of neoantigens or cryptic antigens on the surface of pluripotent hematopoietic stem cells with subsequent activation of immune effector cells and induction of stem cell apoptosis. Histopathological findings obtained from bone marrow biopsy are crucial for diagnosis of AA...
2018: Vnitr̆ní Lékar̆ství
Robert O Dillman
Signal transduction inhibitors and anticheckpoint antibodies have significantly improved survival for metastatic melanoma patients, but most still die within 5 years. Vaccine approaches to induce immunity to well-characterized melanoma-associated antigens, or to antigens expressed on allogeneic tumor cell lines, have not resulted in approved agents. Despite the limitations associated with the immunosuppressive tumor microenvironment, there now is one intralesional autologous vaccine approved for patients who have primarily soft-tissue metastases...
December 2017: Melanoma Management
Laura K Schoch, Kenneth R Cooke, Nina D Wagner-Johnston, Ivana Gojo, Lode J Swinnen, Philip Imus, Ephraim J Fuchs, Mark Levis, Richard F Ambinder, Richard J Jones, Douglas E Gladstone
Published reports suggest that immune checkpoint inhibitors (ICIs) before allogeneic blood or marrow transplantation (alloBMT) may increase the incidence of graft-versus-host disease (GvHD), immune-related adverse events, and nonrelapse mortality (NRM); this led to the US Food and Drug Administration issuing a "Warning and Precaution" regarding the potential for life-threatening immune-mediated complications associated with alloBMT after nivolumab and pembrolizumab. We retrospectively reviewed the outcomes of 14 consecutive patients who received ICIs as their final salvage therapy before T-cell-replete alloBMT using reduced-intensity conditioning...
September 11, 2018: Blood Advances
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