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https://www.readbyqxmd.com/read/29571344/graft-versus-tumor-effect-in-adenocarcinoma-of-the-lung
#1
Daniel C Wiener, Carlos E Bravo-Iñiguez, Vincent Trien-Vihn Ho, Xiaohua Qian, Michael T Jaklitsch
Donor T cells after allogeneic hematopoietic cell transplantation can give rise to the graft-versus-tumor (GVT) effect in hematologic malignancies. GVT effect has been reported previously to cause regression of some solid tumors. However, none have reported a documented case of GVT effect leading to complete resolution of adenocarcinoma of the lung. Here, we present the case of complete regression of a pathologically proven adenocarcinoma of the lung in a patient undergoing myeloablative-matched unrelated donor peripheral blood stem cell transplantation for the treatment of acute myelogenous leukemia...
April 2018: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/29445008/blockade-of-host-%C3%AE-2-adrenergic-receptor-enhances-graft-versus-tumor-effect-through-modulating-apcs
#2
Hemn Mohammadpour, Rachel O'Neil, Jingxin Qiu, Philip L McCarthy, Elizabeth A Repasky, Xuefang Cao
Allogeneic hematopoietic cell transplantation is a potential curative therapy for hematologic malignancies. Host APCs are pivotal to the desired graft-versus-tumor (GVT) effect. Recent studies have shown that β2-adrenergic receptor (β2AR) signaling can have an important impact on immune cell function, including dendritic cells (DCs). In this article, we demonstrate that pretreatment of host mice with a β2AR blocker significantly increases the GVT effect of donor CD8+ T cells by decreasing tumor burden without increasing graft-versus-host disease...
April 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29399396/serine-protease-inhibitor-6-protects-alloreactive-t-cells-from-granzyme-b-mediated-mitochondrial-damage-without-affecting-graft-versus-tumor-effect
#3
Wei Du, Hemn Mohammadpour, Rachel E O'Neill, Sandeep Kumar, Chuan Chen, Michelle Qiu, Lin Mei, Jingxin Qiu, Philip L McCarthy, Kelvin P Lee, Xuefang Cao
Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy for hematologic malignancies. Donor T cells are able to eliminate residual tumor cells after allo-HCT, producing the beneficial graft-versus-tumor (GVT) effect, but can also cause graft-versus-host disease (GVHD) when attacking host normal tissues. We previously reported that granzyme B (GzmB) is involved in activation-induced cell death (AICD) of donor T cells and exerts differential impacts on GVHD and GVT effect. Serine protease inhibitor 6 (Spi6) is the sole endogenous inhibitor of GzmB that can protect immune and tissue cells against GzmB-mediated damage...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29362503/alloantigen-expression-on-malignant-cells-and-healthy-host-tissue-influences-graft-versus-tumor-reactions-after-allogeneic-hematopoietic-stem-cell-transplantation
#4
Stella Robert, Jörn C Albring, Karin Frebel, Corinna Opitz, Jennifer Urh, Claudia Wolf, Christine Heinrich, Wolfgang E Berdel, Matthias Stelljes
Durable remissions of hematological malignancies regularly observed following allogeneic hematopoietic stem cell transplantation (aHSCT) are due to the conditioning regimen, as well as an immunological phenomenon called graft-versus-leukemia (GVL) or graft-versus-tumor (GVT) effect. The development of GVL is closely linked to graft-versus-host disease (GVHD), the main side effect associated with aHSCT. Both, GVHD and GVL are mediated by donor T cells that are initially activated by antigen-presenting cells that present recipient-derived alloantigens in the context of either matched or mismatched MHC class I molecules...
January 23, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29222323/graft-versus-tumor-effects-and-why-people-relapse
#5
REVIEW
J H Frederik Falkenburg, Inge Jedema
Graft-versus-tumor (GVT) reactivity mediated by donor T cells in the context of allogeneic stem cell transplantation (alloSCT) is one of the most potent forms of cellular immunotherapy. The antitumor effect against hematologic malignancies is mediated by a polyclonal T-cell response targeting polymorphic antigens expressed on hematopoietic tissues of the recipient, leaving donor hematopoiesis in the patient after transplantation unharmed. Fortunately, hematopoietic tissues (including malignant hematopoietic cell populations) are relatively susceptible to T-cell recognition...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29082329/a-rare-case-report-of-hydronephrosis-and-acute-kidney-injury-secondary-to-gonadal-vein-thrombosis-in-a-young-male
#6
Jason M Sandberg, Raymond B Dyer, Majid Mirzazadeh
Background: Gonadal vein thrombosis (GVT) has been reported in association with malignancy and pelvic inflammatory conditions. Patients who develop GVT often require systemic anticoagulation to reduce the risk of pulmonary embolism and other local and distant thromboembolic effects. As the gonadal vein courses from the pelvis toward its outlet in the upper abdomen, its intimate relationship to the ureter in the setting of vascular pathology may pose a risk for urinary obstruction in the adult. We are reporting a rare case of GVT leading to ureteral obstruction and acute kidney injury (AKI) in a young otherwise healthy male and provide a review of similar literature...
2017: Journal of Endourology Case Reports
https://www.readbyqxmd.com/read/28971659/-hematopoietic-stem-cell-transplantation-in-the-perspective-of-time-and-up-to-the-2000-transplant-at-the-rambam-health-care-campus
#7
REVIEW
Israel Henig, Jacob Rowe, Nuhad Hadad, Riva Fineman, Noam Benyamini, Tsila Zuckerman
Stem cell transplantation is indicated in hematological malignancies as well as some solid tumors and congenital abnormalities. Autologous transplantation allows the administration of high dose chemotherapy without prolonged bone marrow aplasia. Allogeneic transplantation allows us to give the patient a new immune system that can locate and destroy remaining tumor cells. First attempts in patients began in 1939. Improved outcomes occurred after discovering the human leukocyte antigen system which allowed for matching the donor to the patient...
September 2017: Harefuah
https://www.readbyqxmd.com/read/28912330/genome-sequence-of-grapevine-virus-t-a-novel-foveavirus-infecting-grapevine
#8
Yeonhwa Jo, Myung-Kyu Song, Hoseong Choi, Jae-Seong Park, Jae-Wung Lee, Sen Lian, Bong Choon Lee, Won Kyong Cho
Here, we report the genome sequence of grapevine virus T (GVT), a novel single-stranded RNA virus identified from a transcriptome of grapevine. The genome of GVT is 8,701 nucleotides in length and encodes five open reading frames. GVT is a putative member of the genus Foveavirus in the family Betaflexiviridae.
September 14, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28751785/ctla4-cd28-chimera-gene-modification-of-t-cells-enhances-the-therapeutic-efficacy-of-donor-lymphocyte-infusion-for-hematological-malignancy
#9
Hyung Bae Park, Ji Eun Lee, Yu Mi Oh, Sang Jin Lee, Hyeon-Seok Eom, Kyungho Choi
Donor lymphocyte infusion (DLI) followed by hematopoietic stem cell transplantation has served as an effective prevention/treatment modality against the relapse of some hematologic tumors, such as chronic myeloid leukemia (CML). However, the therapeutic efficacies of DLI for other types of leukemia, including acute lymphocytic leukemia (ALL), have been limited thus far. Therefore, we examined whether increasing the reactivity of donor T cells by gene modification could enhance the therapeutic efficacy of DLI in a murine model of ALL...
July 28, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28724800/siglec-g-represses-damp-mediated-effects-on-t-cells
#10
Tomomi Toubai, Corinne Rossi, Katherine Oravecz-Wilson, Cynthia Zajac, Chen Liu, Thomas Braun, Hideaki Fujiwara, Julia Wu, Yaping Sun, Stuart Brabbs, Hiroya Tamaki, John Magenau, Pang Zheng, Yang Liu, Pavan Reddy
The role of negative regulators or suppressors of the damage-associated molecular pattern-mediated (DAMP-mediated) stimulation of innate immune responses is being increasingly appreciated. However, the presence and function of suppressors of DAMP-mediated effects on T cells, and whether they can be targeted to mitigate T cell-dependent immunopathology remain unknown. Sialic acid-binding immunoglobulin-like lectin G (Siglec-G) is a negative regulator of DAMP-mediated responses in innate immune cells, but its T cell-autonomous role is unknown...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28637876/monocyte-derived-dendritic-cells-with-silenced-pd-1-ligands-and-transpresenting-interleukin-15-stimulate-strong-tumor-reactive-t-cell-expansion
#11
Johan M J Van den Bergh, Evelien L J M Smits, Zwi N Berneman, Tim J A Hutten, Hans De Reu, Viggo F I Van Tendeloo, Harry Dolstra, Eva Lion, Willemijn Hobo
Although allogeneic stem cell transplantation (allo-SCT) can elicit graft-versus-tumor (GVT) immunity, patients often relapse due to residual tumor cells. As essential orchestrators of the immune system, vaccination with dendritic cells (DC) is an appealing strategy to boost the GVT response. Nevertheless, durable clinical responses after DC vaccination are still limited, stressing the need to improve current DC vaccines. Aiming to empower DC potency, we engineered monocyte-derived DCs to deprive them of ligands for the immune checkpoint regulated by programmed death 1 (PD-1)...
August 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28615039/interleukin-21-promotes-thymopoiesis-recovery-following-hematopoietic-stem-cell-transplantation
#12
Aurélie Tormo, Fatemeh Khodayarian, Yun Cui, Edouard Al-Chami, Reem Kanjarawi, Beatriz Noé, Huijie Wang, Moutih Rafei
BACKGROUND: Impaired T cell reconstitution remains a major deterrent in the field of bone marrow (BM) transplantation (BMT) due to pre-conditioning-induced damages inflicted to the thymi of recipient hosts. Given the previously reported thymo-stimulatory property of interleukin (IL)-21, we reasoned that its use post-BMT could have a profound effect on de novo T cell development. METHODS: To evaluate the effect of IL-21 on de novo T cell development in vivo, BM derived from RAG2p-GFP mice was transplanted into LP/J mice...
June 14, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28588699/irradiation-of-peripheral-blood-mononuclear-cells-with-7-5-gy-x-rays-prior-to-donor-lymphocyte-infusion-inhibits-proliferation-while-preserving-cytotoxicity-and-improves-the-effectiveness-of-hsct-in-patients-with-hematological-malignancies
#13
Yong-Qiu Wei, Xi-Nan Cen, Hui-Hui Liu, Yu-Hua Sun, Yong-Jin Shi, Wei Liu, Yu-Jun Dong, Han-Yun Ren
The aim of the present study was to explore the effect of different X-ray doses on the proliferation and cytotoxic activity of peripheral blood mononuclear cells (PBMCs), particularly lymphocytes, in order to assess whether this reduces the incidence of graft vs. host disease (GVHD) while preserving the graft vs. tumor (GVT) effect in patients with hematological malignancies following hematopoietic stem cell transplantation (HSCT). PBMCs from healthy donors were irradiated with X-rays at doses of 0, 2.5, 5, 7...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28574833/new-interleukin-15-superagonist-il-15sa-significantly-enhances-graft-versus-tumor-activity
#14
Cavan P Bailey, Tulin Budak-Alpdogan, Christopher T Sauter, Michelle M Panis, Cihangir Buyukgoz, Emily K Jeng, Hing C Wong, Neal Flomenberg, Onder Alpdogan
Interleukin-15 (IL-15) is a potent cytokine that increases CD8+ T and NK cell numbers and function in experimental models. However, obstacles remain in using IL-15 therapeutically, specifically its low potency and short in vivo half-life. To help overcome this, a new IL-15 superagonist complex comprised of an IL-15N72D mutation and IL-15RαSu/Fc fusion (IL-15SA, also known as ALT-803) was developed. IL-15SA exhibits a significantly longer serum half-life and increased in vivo activity against various tumors...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28405517/hematopoietic-stem-cell-derived-myeloid-and-plasmacytoid-dc-based-vaccines-are-highly-potent-inducers-of-tumor-reactive-t-cell-and-nk-cell-responses-ex-vivo
#15
Soley Thordardottir, Nicolaas Schaap, Elja Louer, Michel G D Kester, J H Frederik Falkenburg, Joop Jansen, Timothy R D Radstake, Willemijn Hobo, Harry Dolstra
Because of the potent graft-versus-tumor (GVT) effect, allogeneic stem cell transplantation (alloSCT) can be a curative therapy for hematological malignancies. However, relapse remains the most frequent cause of treatment failure, illustrating the necessity for development of adjuvant post-transplant therapies to boost GVT immunity. Dendritic cell (DC) vaccination is a promising strategy in this respect, in particular, where distinct biologic functions of naturally occurring DC subsets, i.e. myeloid DCs (mDCs) and plasmacytoid DCs (pDCs), are harnessed...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28229282/clinical-studies-in-hematologic-microtransplantation
#16
REVIEW
Kevin A David, Dennis Cooper, Roger Strair
The anti-tumor effects of allogeneic hematopoietic stem cell transplantation depend upon engraftment of donor cells followed by a graft-versus-tumor (GVT) effect. However, pre-clinical and clinical studies have established that under certain circumstances, anti-tumor responses can occur despite the absence of high levels of durable donor cell engraftment. Tumor response with little or no donor engraftment has been termed "microtransplantation." It has been hard to define conditions leading to tumor responses without donor cell persistence in humans because the degree of engraftment depends very heavily upon many patient-specific factors, including immune status and degree of prior therapy...
February 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28064242/cyclin-dependent-kinase-5-activity-is-required-for-allogeneic-t-cell-responses-after-hematopoietic-cell-transplantation-in-mice
#17
David Askew, Tej K Pareek, Saada Eid, Sudipto Ganguly, Megan Tyler, Alex Y Huang, John J Letterio, Kenneth R Cooke
Molecular intermediates in T-cell activation pathways are crucial targets for the therapy and prevention of graft-versus-host disease (GVHD) following allogeneic hematopoietic cell transplantation (allo-HCT). We recently identified an essential role for cyclin-dependent kinase 5 (Cdk5) in T-cell activation and effector function, but the contribution of Cdk5 activity to the development of GVHD has not been explored. Using an established, preclinical, murine, GVHD model, we reveal that Cdk5 activity is increased in key target organs early after allo-HCT...
January 12, 2017: Blood
https://www.readbyqxmd.com/read/28058217/review-of-allogeneic-hematopoietic-stem-cell-transplantation-with-reduced-intensity-conditioning-in-solid-tumors-excluding-breast-cancer
#18
REVIEW
Nuri Karadurmus, Ugur Sahin, Bilgin Bahadir Basgoz, Fikret Arpaci, Taner Demirer
Solid tumors in adults constitute a heterogeneous group of malignancy originating from various organ systems. Solid tumors are not completely curable by chemotherapy, even though some subgroups are very chemo-sensitive. Recently, oncologists have focused on the use of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with reduced intensity conditioning (RIC) for the treatment of some refractory solid tumors. After the demonstration of allogeneic graft-versus-leukemia effect in patients with hematological malignancies who received allo-HSCT, investigators evaluated this effect in patients with refractory metastatic solid tumors...
December 24, 2016: World Journal of Transplantation
https://www.readbyqxmd.com/read/28012219/incorporation-of-high-dose-131-i-metaiodobenzylguanidine-treatment-into-killer-immunoglobulin-like-receptor-hla-ligand-mismatched-haploidentical-stem-cell-transplantation-for-children-with-neuroblastoma-who-failed-tandem-autologous-stem-cell-transplantation
#19
Ji Won Lee, Eun-Suk Kang, Ki Woong Sung, Eunsang Yi, Soo Hyun Lee, Keon Hee Yoo, Hong Hoe Koo
BACKGROUND: We performed a pilot study (NCT 00793351) to evaluate the effectiveness and feasibility of a strategy incorporating high-dose (131) I-metaiodobenzylguanidine (HD-MIBG) treatment into killer immunoglobulin-like receptor (KIR)/HLA-ligand mismatched haploidentical stem cell transplantation (haplo-SCT) in improving the survival of children with neuroblastoma who failed previous tandem autologous SCT. PROCEDURE: If the patient remained progression free with salvage treatment, HD-MIBG treatment (18 mCi/kg) was given prior to reduced-intensity conditioning (cyclophosphamide + fludarabine + antithymocyte globulin)...
June 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27997582/-gt-n-repeat-polymorphism-in-heme-oxygenase-1-ho-1-correlates-with-clinical-outcome-after-myeloablative-or-nonmyeloablative-allogeneic-hematopoietic-cell-transplantation
#20
COMPARATIVE STUDY
Tania Køllgaard, Brian Kornblit, Jesper Petersen, Tobias Wirenfeldt Klausen, Bo Kok Mortensen, Peter Brændstrup, Henrik Sengeløv, Estrid Høgdall, Klaus Müller, Lars Vindeløv, Mads Hald Andersen, Per Thor Straten
Allogeneic hematopoietic cell transplantation (HCT) is a treatment for various hematologic diseases where efficacy of treatment is in part based on the graft versus tumour (GVT) activity of cells in the transplant. The cytoprotective enzyme heme oxygenase-1 (HO-1) is a rate-limiting enzyme in heme degradation and it has been shown to exert anti-inflammatory functions. In humans a (GT)n repeat polymorphism regulates the expression of HO-1. We conducted fragment length analyses of the (GT)n repeat in the promotor region of the gene for HO-1 in DNA from donors and recipients receiving allogeneic myeloablative- (MA) (n = 110) or nonmyeloablative- (NMA-) (n = 250) HCT...
2016: PloS One
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