keyword
https://read.qxmd.com/read/37690238/dominant-negative-tgf%C3%AE-receptor-ii-and-truncated-tim3-enhance-the-antitumor-efficacy-of-car-t-cell-therapy-in-prostate-cancer
#1
JOURNAL ARTICLE
Lei Tang, Huimin Shao, Yao Wu, Jiawei Wang, Xueyi Qian, Lianjun He, Houbao Huang, Zhenyu Xu
BACKGROUND: The immune checkpoint molecules, Transforming growth factor beta receptor II (TGFβRII) and T cell immunoglobulin and mucin domain 3 (TIM3), have been identified as contributors to T cell immune suppression in prostate cancer. The objective of this investigation was to improve the tumor killing capability of prostate-specific membrane antigen (PSMA)-chimeric antigen receptor T (CAR-T) cells by targeting TIM3 and TGFβRII simultaneously. METHODS: To generate dnTGFβRII-trTIM3-PSMA-CAR-T (DT-PSMA-CAR-T) cells, the surface of PSMA-CAR-T cells was overexpressed with dominant negative TGFβRII (dnTGFβRII) and truncated extracellular TIM3 (trTIM3)...
September 8, 2023: International Immunopharmacology
https://read.qxmd.com/read/37052811/therapeutic-targets-in-myelodysplastic-neoplasms-beyond-hypomethylating-agents
#2
REVIEW
Prateek Pophali, Sudhamsh Reddy Desai, Aditi Shastri
PURPOSE OF REVIEW: To discuss novel targeted therapies under investigation for treatment of myelodysplastic neoplasms (MDS). RECENT FINDINGS: Over the last few years, results of phase 3 trials assessing novel therapies for high-risk MDS have been largely disappointing. Pevonedistat (NEDD-8 inhibitor) and APR-246 (TP53 reactivator) both did not meet trial endpoints. However, early phase trials of BCL-2, TIM3, and CD47 inhibitors have shown exciting data and are currently under phase 3 investigation...
June 2023: Current Hematologic Malignancy Reports
https://read.qxmd.com/read/36972454/tonic-signaling-chimeric-antigen-receptors-drive-human-regulatory-t-cell-exhaustion
#3
JOURNAL ARTICLE
Caroline Lamarche, Kirsten Ward-Hartstonge, Tian Mi, David T S Lin, Qing Huang, Andrew Brown, Karlie Edwards, Gherman E Novakovsky, Christopher N Qi, Michael S Kobor, Caitlin C Zebley, Evan W Weber, Crystal L Mackall, Megan K Levings
Regulatory T cell (Treg) therapy is a promising approach to improve outcomes in transplantation and autoimmunity. In conventional T cell therapy, chronic stimulation can result in poor in vivo function, a phenomenon termed exhaustion. Whether or not Tregs are also susceptible to exhaustion, and if so, if this would limit their therapeutic effect, was unknown. To "benchmark" exhaustion in human Tregs, we used a method known to induce exhaustion in conventional T cells: expression of a tonic-signaling chimeric antigen receptor (TS-CAR)...
April 4, 2023: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/36532017/distinctive-phenotype-for-hla-e-versus-hla-a2-restricted-memory-cd8-%C3%AE-%C3%AE-t-cells-in-the-course-of-hcmv-infection-discloses-features-shared-with-nkg2c-cd57-nk-and-%C3%AE-2-%C3%AE-%C3%AE-t-cell-subsets
#4
JOURNAL ARTICLE
Amélie Rousselière, Nathalie Gérard, Laurence Delbos, Pierrick Guérif, Magali Giral, Céline Bressollette-Bodin, Béatrice Charreau
The human cytomegalovirus (HCMV) triggers both innate and adaptive immune responses, including protective CD8+ αβT cells (CD8T) that contributes to the control of the infection. In addition to CD8T restricted by classical HLA class Ia molecules, HCMV also triggers CD8T recognizing peptides from the HCMV UL40 leader peptide and restricted by HLA-E molecules (HLA-EUL40 CD8T). This study investigated the frequency, phenotype and functions of HLA-EUL40 CD8T in comparison to the immunodominant HLA-A2pp65 CD8T upon acute (primary or secondary infection) or chronic infection in kidney transplant recipients (KTR) and in seropositive (HCMV+ ) healthy volunteer (HV) hosts...
2022: Frontiers in Immunology
https://read.qxmd.com/read/35320468/new-approaches-to-myelodysplastic-syndrome-treatment
#5
REVIEW
Alexandre Bazinet, Guillermo Montalban Bravo
The treatment of myelodysplastic syndromes (MDS) begins with risk stratification using a validated tool such as the International Prognostic Scoring System (IPSS) or its revised version (IPSS-R). This divides patients into lower- and higher- risk categories. Although treatment objectives in lower-risk MDS (LR-MDS) have traditionally been directed at improving cytopenias (usually anemia) as well as quality of life, recent data supports a potential role for early intervention in delaying transfusion dependency...
May 2022: Current Treatment Options in Oncology
https://read.qxmd.com/read/34914826/blinatumomab-maintenance-after-allogeneic-hematopoietic-cell-transplantation-for-b-lineage-acute-lymphoblastic-leukemia
#6
JOURNAL ARTICLE
Mahmoud R Gaballa, Pinaki Banerjee, Denái R Milton, Xianli Jiang, Christina Ganesh, Sajad Khazal, Vandana Nandivada, Sanjida Islam, Mecit Kaplan, May Daher, Rafet Basar, Amin Alousi, Rohtesh Mehta, Gheath Alatrash, Issa Khouri, Betul Oran, David Marin, Uday Popat, Amanda Olson, Priti Tewari, Nitin Jain, Elias Jabbour, Farhad Ravandi, Hagop Kantarjian, Ken Chen, Richard Champlin, Elizabeth Shpall, Katayoun Rezvani, Partow Kebriaei
Patients with B-lineage acute lymphoblastic leukemia (ALL) are at high-risk for relapse after allogeneic hematopoietic cell transplantation (HCT). We conducted a single-center phase 2 study evaluating the feasibility of 4 cycles of blinatumomab administered every 3 months during the first year after HCT in an effort to mitigate relapse in high-risk ALL patients. Twenty-one of 23 enrolled patients received at least 1 cycle of blinatumomab and were included in the analysis. The median time from HCT to the first cycle of blinatumomab was 78 days (range, 44 to 105)...
March 24, 2022: Blood
https://read.qxmd.com/read/34041025/immunotherapy-in-acute-myeloid-leukemia-where-we-stand
#7
REVIEW
Alessandro Isidori, Claudio Cerchione, Naval Daver, Courtney DiNardo, Guillermo Garcia-Manero, Marina Konopleva, Elias Jabbour, Farhad Ravandi, Tapan Kadia, Adolfo de la Fuente Burguera, Alessandra Romano, Federica Loscocco, Giuseppe Visani, Giovanni Martinelli, Hagop Kantarjian, Antonio Curti
In the past few years, our improved knowledge of acute myeloid leukemia (AML) pathogenesis has led to the accelerated discovery of new drugs and the development of innovative therapeutic approaches. The role of the immune system in AML development, growth and recurrence has gained increasing interest. A better understanding of immunological escape and systemic tolerance induced by AML blasts has been achieved. The extraordinary successes of immune therapies that harness the power of T cells in solid tumors and certain hematological malignancies have provided new stimuli in this area of research...
2021: Frontiers in Oncology
https://read.qxmd.com/read/33746972/the-role-of-immune-checkpoint-molecules-for-relapse-after-allogeneic-hematopoietic-cell-transplantation
#8
REVIEW
Natalie Köhler, Dietrich Alexander Ruess, Rebecca Kesselring, Robert Zeiser
Immune checkpoint molecules represent physiological brakes of the immune system that are essential for the maintenance of immune homeostasis and prevention of autoimmunity. By inhibiting these negative regulators of the immune response, immune checkpoint blockade can increase anti-tumor immunity, but has been primarily successful in solid cancer therapy and Hodgkin lymphoma so far. Allogeneic hematopoietic cell transplantation (allo-HCT) is a well-established cellular immunotherapy option with the potential to cure hematological cancers, but relapse remains a major obstacle...
2021: Frontiers in Immunology
https://read.qxmd.com/read/33435153/alterations-of-nk-cell-phenotype-in-the-disease-course-of-multiple-myeloma
#9
JOURNAL ARTICLE
Tatiana Pazina, Alexander W MacFarlane, Luca Bernabei, Essel Dulaimi, Rebecca Kotcher, Clinton Yam, Natalie A Bezman, Michael D Robbins, Eric A Ross, Kerry S Campbell, Adam D Cohen
Accumulating evidence demonstrates important roles for natural killer (NK) cells in controlling multiple myeloma (MM). A prospective flow cytometry-based analysis of NK cells in the blood and bone marrow (BM) of MM patient subgroups was performed (smoldering (SMM), newly diagnosed (ND), relapsed/refractory, (RR) and post-stem cell transplantation (pSCT)). Assessments included the biomarker expression and function of NK cells, correlations between the expression of receptors on NK cells with their ligands on myeloma cells, and comparisons between MM patient subgroups and healthy controls...
January 10, 2021: Cancers
https://read.qxmd.com/read/32961369/clinical-grade-expanded-regulatory-t-cells-are-enriched-with-highly-suppressive-cells-producing-il-10-granzyme-b-and-il-35
#10
JOURNAL ARTICLE
Francesca Ulbar, Ida Villanova, Raffaella Giancola, Stefano Baldoni, Francesco Guardalupi, Bianca Fabi, Paola Olioso, Anita Capone, Rosaria Sola, Sara Ciardelli, Beatrice Del Papa, Antonello Brattelli, Ilda Ricciardi, Stefano Taricani, Giulia Sabbatinelli, Ornella Iuliani, Cecilia Passeri, Paolo Sportoletti, Stella Santarone, Antonio Pierini, Giuseppe Calabrese, Franca Falzetti, Tiziana Bonfini, Patrizia Accorsi, Loredana Ruggeri, Massimo Fabrizio Martelli, Andrea Velardi, Mauro Di Ianni
In the setting of T cell-depleted, full-haplotype mismatched transplantation, adoptive immunotherapy with regulatory T cells (Tregs) and conventional T cells (Tcons) can prevent graft-versus-host disease (GVHD) and improve post-transplantation immunologic reconstitution and is associated with a powerful graft-versus-leukemia effect. To improve the purity and the quantity of the infused Tregs, good manufacturing practices (GMP)-compatible expansion protocols are needed. Here we expanded Tregs using an automated, clinical-grade protocol...
December 2020: Biology of Blood and Marrow Transplantation
https://read.qxmd.com/read/32885223/prognostic-plasma-biomarkers-of-early-complications-and-graft-versus-host-disease-in-patients-undergoing-allogeneic-hematopoietic-stem-cell-transplantation
#11
JOURNAL ARTICLE
Balaji Balakrishnan, Raveen Stephen Stallon Illangeswaran, Bharathi M Rajamani, Aswin Anand Pai, Infencia Xavier Raj, Daniel Zechariah Paul, Kavitha Lakshmi, Thenmozhi Mani, Ezhilpavai Mohanan, Uday Kulkarni, Anup Joseph Devasia, N A Fouzia, Anu Korula, Aby Abraham, Alok Srivastava, Vikram Mathews, Sophie Paczesny, Biju George, Poonkuzhali Balasubramanian
Early complications post hematopoietic stem cell transplantation (HSCT) such as sinusoidal obstruction syndrome (SOS) and graft versus host disease (GVHD) can be life threatening. Although several biomarkers have been identified to correlate with these complications and their response to treatment, these are yet to be used in clinical practice. Here, we evaluated circulating endothelial cells (CECs) (n = 26) and plasma biomarkers (ST2, REG3 α , VCAM1, ICAM1, TIM3) (N = 210) at early time points, to determine their association with early complications post-HSCT...
July 2020: EJHaem
https://read.qxmd.com/read/32581055/il-6-promotes-pd-l1-expression-in-monocytes-and-macrophages-by-decreasing-protein-tyrosine-phosphatase-receptor-type-o-expression-in-human-hepatocellular-carcinoma
#12
JOURNAL ARTICLE
Wenjie Zhang, Yang Liu, Zhongyi Yan, Hui Yang, Wei Sun, Yongliang Yao, Yun Chen, Runqiu Jiang
BACKGROUND: We have previously discovered a relationship between the low expression of protein tyrosine phosphatase, receptor type O (PTPRO) in tumor-infiltrating T cells and immunosuppression. The aim of the present study was to investigate the relationship between decreased PTPRO and increased programmed death ligand 1 (PD-L1) in both the peripheral monocytes and tumor-infiltrating macrophages of human hepatocellular carcinoma (HCC). METHODS: The expression and correlation of all the indices were explored in monocytes and tumor-infiltrating macrophages within both human and mice HCC...
June 2020: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/31678540/inflammatory-cytokine-profile-in-individuals-with-inherited-chromosomally-integrated-human-herpesvirus-6
#13
JOURNAL ARTICLE
Daniel P Weschke, Wendy M Leisenring, Richard L Lawler, Terry Stevens-Ayers, Meei-Li Huang, Keith R Jerome, Danielle M Zerr, John A Hansen, Michael Boeckh, Joshua A Hill
Acute graft-versus-host-disease (aGVHD) is a major complication following hematopoietic cell transplantations (HCTs). We have shown that HCT recipients in whom either the donor or patient had inherited chromosomally integrated human herpesvirus 6 (iciHHV-6) have a higher incidence of developing more severe aGVHD. Previous studies established that increased proinflammatory cytokines are associated with increased risk for aGVHD and nonrelapse mortality post-HCT. We hypothesized that HCT recipients with donor or recipient iciHHV-6 (iciHHV-6pos HCT cases) will have higher cytokine levels compared with HCT recipients without iciHHV-6 (iciHHV-6neg HCT controls)...
October 31, 2019: Biology of Blood and Marrow Transplantation
https://read.qxmd.com/read/31678303/disruption-of-sirt7-increases-the-efficacy-of-checkpoint-inhibitor-via-mef2d-regulation-of-programmed-cell-death-1-ligand-1-in-hepatocellular-carcinoma-cells
#14
JOURNAL ARTICLE
Junyu Xiang, Ni Zhang, Hui Sun, Li Su, Chengcheng Zhang, Huailong Xu, Juan Feng, Meiling Wang, Jun Chen, Limei Liu, Juanjuan Shan, Junjie Shen, Zhi Yang, Guiqin Wang, Haijun Zhou, Jesus Prieto, Matías A Ávila, Chungang Liu, Cheng Qian
BACKGROUND & AIMS: Immune checkpoint inhibitors have some efficacy in the treatment of hepatocellular carcinoma (HCC). Programmed cell death 1 ligand 1 (PD-L1), expressed on some cancer cells, binds to the receptor programmed cell death 1 (PDCD1, also called PD1) on T cells to prevent their proliferation and reduce the antigen-tumor immune response. Immune cells that infiltrate some types of HCCs secrete interferon gamma (IFNG). Some HCC cells express myocyte enhancer factor 2D (MEF2D), which has been associated with shorter survival times of patients...
February 2020: Gastroenterology
https://read.qxmd.com/read/31445183/t-cell-transcriptional-profiling-and-immunophenotyping-uncover-lag3-as-a-potential-significant-target-of-immune-modulation-in-multiple-myeloma
#15
JOURNAL ARTICLE
Fabienne Lucas, Michael Pennell, Ying Huang, Don M Benson, Yvonne A Efebera, Maria Chaudhry, Tiffany Hughes, Jennifer A Woyach, John C Byrd, Suohui Zhang, Desiree Jones, Xiangnan Guan, Christin E Burd, Ashley E Rosko
Autologous stem cell transplant (ASCT) is the standard of care for patients with multiple myeloma (MM). The clinical significance of peripheral blood T lymphocyte (PBTL) immunologic changes associated with ASCT is poorly understood. Here we evaluated T cell transcriptional messenger RNA profiles and immunophenotypes to correlate immunologic senescence, exhaustion, and anergy with clinical endpoints in a cohort of patients with MM undergoing ASCT. ASCT induced global transcriptional T cell changes and altered molecular levels of markers of T cell subtypes, T cell activation, and exhaustion...
January 2020: Biology of Blood and Marrow Transplantation
https://read.qxmd.com/read/31024575/bkv-clearance-time-correlates-with-exhaustion-state-and-t-cell-receptor-repertoire-shape-of-bkv-specific-t-cells-in-renal-transplant-patients
#16
JOURNAL ARTICLE
Ulrik Stervbo, Mikalai Nienen, Benjamin J D Weist, Leon Kuchenbecker, Jochen Hecht, Patrizia Wehler, Timm H Westhoff, Petra Reinke, Nina Babel
Reactivation of the BK polyomavirus is known to lead to severe complications in kidney transplant patients. The current treatment strategy relies on decreasing the immunosuppression to allow the immune system to clear the virus. Recently, we demonstrated a clear association between the resolution of BKV reactivation and reconstitution of BKV-specific CD4+ T-cells. However, which factors determine the duration of viral infection clearance remains so far unclear. Here we apply a combination of in-depth multi-parametric flow cytometry and NGS-based CDR3 beta chain receptor repertoire analysis of BKV-specific T-cells to a cohort of 7 kidney transplant patients during the clinical course of BKV reactivation...
2019: Frontiers in Immunology
https://read.qxmd.com/read/30292745/over-expression-of-pd-1-does-not-predict-leukemic-relapse-after-allogeneic-stem-cell-transplantation
#17
JOURNAL ARTICLE
Prachi Jain, Xin Tian, Stefan Cordes, Jinguo Chen, Caroline R Cantilena, Christian Bradley, Reema Panjwani, Fariba Chinian, Keyvan Keyvanfar, Minoo Battiwalla, Pawel Muranski, A John Barrett, Sawa Ito
Blockade of the T-cell exhaustion marker PD-1 to re-energize the immune response is emerging as a promising cancer treatment. Relapse of hematologic malignancy after allogeneic stem cell transplantation limits the success of this approach, and PD-1 blockade may hold therapeutic promise. However, PD-1 expression and its relationship with post-transplant relapse is poorly described. Because the donor immunity is activated by alloresponses, PD-1 expression may differ from nontransplanted individuals, and PD-1 blockade could risk graft-versus-host disease...
February 2019: Biology of Blood and Marrow Transplantation
https://read.qxmd.com/read/27827824/plasma-biomarkers-of-risk-for-death-in-a-multicenter-phase-3-trial-with-uniform-transplant-characteristics-post-allogeneic-hct
#18
RANDOMIZED CONTROLLED TRIAL
Mohammad Abu Zaid, Juan Wu, Cindy Wu, Brent R Logan, Jeffrey Yu, Corey Cutler, Joseph H Antin, Sophie Paczesny, Sung Won Choi
A phase 3 clinical trial (BMT CTN 0402) comparing tacrolimus/sirolimus (Tac/Sir) vs tacrolimus/methotrexate (Tac/Mtx) as graft-versus-host disease (GVHD) prophylaxis after matched-related allogeneic hematopoietic cell transplantation (HCT) recently showed no difference between study arms in acute GVHD-free survival. Within this setting of a prospective, multicenter study with uniform GVHD prophylaxis, conditioning regimen, and donor source, we explored the correlation of 10 previously identified biomarkers with clinical outcomes after allogeneic HCT...
January 12, 2017: Blood
https://read.qxmd.com/read/27458246/antitumor-effect-of-programmed-death-1-pd-1-blockade-in-humanized-the-nog-mhc-double-knockout-mouse
#19
JOURNAL ARTICLE
Tadashi Ashizawa, Akira Iizuka, Chizu Nonomura, Ryota Kondou, Chie Maeda, Haruo Miyata, Takashi Sugino, Koichi Mitsuya, Nakamasa Hayashi, Yoko Nakasu, Kouji Maruyama, Ken Yamaguchi, Ikumi Katano, Mamoru Ito, Yasuto Akiyama
PURPOSE: Humanized mouse models using NOD/Shi-scid-IL2rγnull (NOG) and NOD/LtSz-scid IL2rγnull (NSG) mouse are associated with several limitations, such as long incubation time for stem cell engraftment and the development of xenograft versus host disease in mice injected with peripheral blood mononuclear cells (PBMCs). To solve problems, we used humanized major histocompatibility class I- and class II-deficient NOG mice (referred to as NOG-dKO) to evaluate the antitumor effect of anti-programmed death-1 (PD-1) antibody...
January 1, 2017: Clinical Cancer Research
https://read.qxmd.com/read/26492394/control-of-immune-response-to-allogeneic-embryonic-stem-cells-by-cd3-antibody-mediated-operational-tolerance-induction
#20
JOURNAL ARTICLE
D Calderon, M Prot, S You, C Marquet, V Bellamy, P Bruneval, F Valette, P de Almeida, J C Wu, M Pucéat, P Menasché, L Chatenoud
Implantation of embryonic stem cells (ESCs) and their differentiated derivatives into allogeneic hosts triggers an immune response that represents a hurdle to clinical application. We established in autoimmunity and in transplantation that CD3 antibody therapy induces a state of immune tolerance. Promising results have been obtained with CD3 antibodies in the clinic. In this study, we tested whether this strategy can prolong the survival of undifferentiated ESCs and their differentiated derivatives in histoincompatible hosts...
February 2016: American Journal of Transplantation
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