Current Research in Translational Medicine最新文献

{"title":"Impact of tixagevimab/cilgavimab prophylaxis in patients undergoing allogeneic hematopoietic stem cell transplants and CAR T-cell therapy: A single center experience","authors":"Elisabetta Xue , Gianluca Scorpio , Annalisa Ruggeri , Daniela Clerici , Francesca Farina , Edoardo Campodonico , Andrea Acerbis , Paolo Fiore , Alessandro Bruno , Matteo G Carrabba , Jacopo Peccatori , Raffaella Greco , Maria Teresa Lupo Stanghellini , Fabio Ciceri , Consuelo Corti","doi":"10.1016/j.retram.2023.103402","DOIUrl":"10.1016/j.retram.2023.103402","url":null,"abstract":"","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"71 3","pages":"Article 103402"},"PeriodicalIF":4.1,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10299847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9811502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum soluble BCMA can be used to monitor relapse of multiple myeloma patients after chimeric antigen receptor T-cell immunotherapy","authors":"Ying Shen ,&nbsp;Jie Liu ,&nbsp;Baiyan Wang ,&nbsp;Yilin Zhang ,&nbsp;Yan Xu ,&nbsp;Xiaman Wang ,&nbsp;Yachun Jia ,&nbsp;Xin Meng ,&nbsp;Xugeng Wang ,&nbsp;Xiaohu Fan ,&nbsp;Aili He ,&nbsp;Wanhong Zhao","doi":"10.1016/j.retram.2023.103378","DOIUrl":"10.1016/j.retram.2023.103378","url":null,"abstract":"<div><h3>Purpose</h3><p><span>Chimeric antigen receptor T-cell (CAR-T) therapy has been proven very effective in treating hematologic malignancies<span><span>. Ciltacabtagene autoleucel (cilta-cel), a second-generation CAR-T cell with double B cell maturation antigen (BCMA) targeting binding domains, showed an 88% overall response rate (ORR) </span>in patients with relapsed/refractory </span></span>multiple myeloma (MM), which were carried out in our institute. This study aimed to assess the prognostic potential of soluble BCMA (sBCMA) in serum as a biomarker in MM after CAR-T therapy.</p></div><div><h3>Patients and methods</h3><p>Serum samples (<em>n</em> = 44) from MM patients were collected before and after CAR-T therapy. The level of sBCMA was analyzed by enzyme-linked immunosorbent assay (ELISA). Additionally, three patients’ long-term longitudinal analysis were performed.</p></div><div><h3>Results</h3><p>Serum sBCMA level was correlated with the percentage of malignant plasma cells in bone marrow (<em>r</em> = 0.613). After CAR-T infusion, the sBCMA level in serum of MM patients decreased markedly (median: 508,513 pg/mL before CAR-T infusion, 89,198 pg/mL in the first month, 8448 pg/mL in the second months, and 6010 pg/mL in the third month after CAR-T infusion). In patients who obtained objective response (≥ PR), re-elevated sBCMA indicated the possibility of disease recurrence. At a cutoff 69,326.27 pg/mL, sBCMA shows high sensitivity (87.5%) and specificity (88.5%) for identifying relapse of MM after CAR-T therapy.</p></div><div><h3>Conclusion</h3><p>Our results suggested that serum sBCMA level changes in response to the clinical status of MM patients after anti-BCMA CAR-T therapy. Furthermore, sBCMA may be a auxiliary biomarker for disease monitoring in MM patients after CAR-T therapy.</p></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"71 2","pages":"Article 103378"},"PeriodicalIF":4.1,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9648318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"mRNA-lncRNA gene expression signature for predicting pediatric AML relapse","authors":"E.D. Kulaeva,&nbsp;E.V. Mashkina","doi":"10.1016/j.retram.2023.103379","DOIUrl":"10.1016/j.retram.2023.103379","url":null,"abstract":"<div><p>Children with acute myeloid leukemia (AML) face a relapse of the disease in 30% of all cases. AML relapse is difficult to predict, and existing risk scales are often ineffective. Using data from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET-AML) project, we defined an expression signature based on matrix RNAs (mRNAs) and long non-coding RNAs (lncRNAs) that could predict relapse in pediatric AML patients.</p><p>We used a comprehensive bioinformatics analysis that included the identification of functionally significant differentially expressed genes in AML relapse, several rounds of association with relapse-free survival (RFS) mRNAs and lncRNAs selection, and evaluation of the obtained expression signatures to predict recurrence at the primary tumor level.</p><p>Two mRNAs (ENSG00000149289.11 (ZC3H12C) and ENSG00000075213.11 (SEMA3A)) and one lncRNA (ENSG00000287569.1) were associated with a decreased RFS. Models including changes in the expression of ZC3H12C and ENSG00000287569.1, as well as all three markers, demonstrated very good quality and could predict the recurrence of pediatric AML.</p></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"71 2","pages":"Article 103379"},"PeriodicalIF":4.1,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9701779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scaling up human mesenchymal stem cell manufacturing using bioreactors for clinical uses","authors":"Marina Gazdic Jankovic ,&nbsp;Miodrag Stojkovic ,&nbsp;Sanja Bojic ,&nbsp;Nemanja Jovicic ,&nbsp;Marina Miletic Kovacevic ,&nbsp;Zeljko Ivosevic ,&nbsp;Aleksandar Juskovic ,&nbsp;Vojin Kovacevic ,&nbsp;Biljana Ljujic","doi":"10.1016/j.retram.2023.103393","DOIUrl":"10.1016/j.retram.2023.103393","url":null,"abstract":"<div><p>Human mesenchymal stem cells (hMSCs) are multipotent cells and an attractive therapeutic agent in regenerative medicine and intensive clinical research. Despite the great potential, the limitation that needs to be overcome is the necessity of <em>ex vivo</em> expansion because of insufficient number of hMSCs presented within adult organs and the high doses required for a transplantation. As a result, numerous research studies aim to provide novel expansion methods in order to achieve appropriate numbers of cells with preserved therapeutic quality. Bioreactor-based cell expansion provide high-level production of hMSCs in accordance with good manufacturing practice (GMP) and quality standards. This review summarizes current knowledge about the hMSCs manufacturing platforms with a main focus to the application of bioreactors for large-scale production of GMP-grade hMSCs.</p></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"71 2","pages":"Article 103393"},"PeriodicalIF":4.1,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10023845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibodies to calnexin and mutated calreticulin are common in human sera","authors":"C Kyllesbech ,&nbsp;N Trier ,&nbsp;F Mughal ,&nbsp;P Hansen ,&nbsp;M Holmström ,&nbsp;D el Fassi ,&nbsp;H Hasselbalch ,&nbsp;V Skov ,&nbsp;L Kjær ,&nbsp;M Andersen ,&nbsp;E Ciplys ,&nbsp;R Slibinskas ,&nbsp;J Frederiksen ,&nbsp;P Højrup ,&nbsp;G Houen","doi":"10.1016/j.retram.2023.103380","DOIUrl":"10.1016/j.retram.2023.103380","url":null,"abstract":"<div><h3>Purpose of the study</h3><p>Calreticulin is an endoplasmic reticulum chaperone protein, which is involved in protein folding and in peptide loading of major histocompatibility complex class I molecules together with its homolog calnexin. Mutated calreticulin is associated with a group of hemopoietic disorders, especially myeloproliferative neoplasms. Currently only the cellular immune response to mutated calreticulin has been described, although preliminary findings have indicated that antibodies to mutated calreticulin are not specific for myeloproliferative disorders. These findings have prompted us to characterize the humoral immune response to mutated calreticulin and its chaperone homologue calnexin.</p></div><div><h3>Patients and methods</h3><p>We analyzed sera from myeloproliferative neoplasm patients, healthy donors and relapsing-remitting multiple sclerosis patients for the occurrence of autoantibodies to wild type and mutated calreticulin forms and to calnexin by enzyme-linked immunosorbent assay.</p></div><div><h3>Results</h3><p>Antibodies to mutated calreticulin and calnexin were present at similar levels in serum samples of myeloproliferative neoplasm and multiple sclerosis patients as well as healthy donors. Moreover, a high correlation between antibodies to mutated calreticulin and calnexin was seen for all patient and control groups. Epitope binding studies indicated that cross-reactive antibodies bound to a three-dimensional epitope encompassing a short linear sequence in the C-terminal of mutated calreticulin and calnexin.</p></div><div><h3>Conclusion</h3><p>Collectively, these findings indicate that calreticulin mutations may be common and not necessarily lead to onset of myeloproliferative neoplasm, possibly due to elimination of cells with mutations. This, in turn, may suggest that additional molecular changes may be required for development of myeloproliferative neoplasm.</p></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"71 2","pages":"Article 103380"},"PeriodicalIF":4.1,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9648325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAR-T cells targeting IL-1RAP produced in a closed semiautomatic system are ready for the first phase I clinical investigation in humans","authors":"Clémentine Nicod ,&nbsp;Mathieu Neto da Rocha ,&nbsp;Walid Warda ,&nbsp;Xavier Roussel ,&nbsp;Rafik Haderbache ,&nbsp;Evan Seffar ,&nbsp;Rim Trad ,&nbsp;Lucie Bouquet ,&nbsp;Mathieu Goncalves ,&nbsp;Léa Bosdure ,&nbsp;Marie-Charlotte Laude ,&nbsp;Mélanie Guiot ,&nbsp;Christophe Ferrand ,&nbsp;Marina Deschamps","doi":"10.1016/j.retram.2023.103385","DOIUrl":"10.1016/j.retram.2023.103385","url":null,"abstract":"<div><h3>Purpose of the study</h3><p>The use of chimeric antigen receptor (CAR)-T cells has demonstrated excellent results in B-lymphoid malignancies. The Advanced Therapy Medicinal Products (ATMP) status and good manufacturing practice (GMP) of CAR-T cells require particular conditions of production performed in a pharmaceutical establishment. Our team developed a new medical drug candidate for acute myeloid leukemia (AML), a CAR targeting interleukin-1 receptor accessory protein (IL-1RAP) expressed by leukemia stem cells, which will need to be evaluated in a phase I-IIa clinical trial. During the preclinical development phase, we produced IL-1RAP CAR-T cells in a semi-automated closed system (CliniMACSࣨ Prodigy) using research grade lentiviral particles.</p></div><div><h3>Patients and the methods</h3><p>The purpose of this work was to validate our production process and to characterize our preclinical GMP-like medicinal product. IL-1RAP CAR-T cells were produced from healthy donors in 9 days, either in an semi-automated closed system (with GMP-like compliant conditions) or according to another research protocols, which was used as a reference.</p></div><div><h3>Results</h3><p>Based on phenotypic, functional and metabolic analyses, we were able to show that the final product is ready for clinical use. Finally, in a xenograft AML murine model, we demonstrated that the IL-1RAP CAR-T cells generated in a GMP-like environment could eliminate tumor cells and increase overall survival.</p></div><div><h3>Conclusion</h3><p>We demonstrated that our IL-1RAP CAR-T cell preclinical GMP-like production process meets standard regulatory requirements in terms of CAR-T cell number, subpopulation phenotype and cytotoxic functionality. Our CAR-T cell production process was validated and can be used to produce medicinal IL-1RAP CAR-T cells for the first phase I clinical trial.</p></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"71 2","pages":"Article 103385"},"PeriodicalIF":4.1,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9647553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Timing of cyclosporine administration for GvHD prophylaxis in haploidentical stem cell transplantation setting: Single center experience","authors":"Jean El Cheikh ,&nbsp;Layal Sharrouf ,&nbsp;Mahdi Hamade ,&nbsp;Khodr Terro ,&nbsp;Ghassan Bidaoui ,&nbsp;Maya Charafeddine ,&nbsp;Fatima Ismail ,&nbsp;Ammar Zahreddine ,&nbsp;Nour Moukalled ,&nbsp;Imane Abou Dalle ,&nbsp;Ali Bazarbachi","doi":"10.1016/j.retram.2023.103387","DOIUrl":"10.1016/j.retram.2023.103387","url":null,"abstract":"","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"71 2","pages":"Article 103387"},"PeriodicalIF":4.1,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9651750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New scenarios in Vacuoles, E1 enzyme, X linked, Autoinflammatory, Somatic (VEXAS) syndrome: Evolution from myelodysplastic syndrome to acute myeloid leukemia","authors":"Giorgia Battipaglia ,&nbsp;Annamaria Vincenzi ,&nbsp;Giulia Falconi ,&nbsp;Alessia Fiore ,&nbsp;Francesco D'Agostino ,&nbsp;Raffaella Iannotta ,&nbsp;Francesco Grimaldi ,&nbsp;Carmelo Gurnari ,&nbsp;Elisa Galossi ,&nbsp;Elena Crisà ,&nbsp;Francesca Bonello ,&nbsp;Giulia Scalia ,&nbsp;Barbara Izzo ,&nbsp;Maria Teresa Voso ,&nbsp;Fabrizio Pane","doi":"10.1016/j.retram.2023.103386","DOIUrl":"10.1016/j.retram.2023.103386","url":null,"abstract":"","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"71 2","pages":"Article 103386"},"PeriodicalIF":4.1,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9702324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory factors involved in Th17/Treg cell balance of immune thrombocytopenia","authors":"Masoud Kargar ,&nbsp;Mehdi Torabizadeh ,&nbsp;Daryush Purrahman ,&nbsp;Zeinab Deris Zayeri ,&nbsp;Najmaldin Saki","doi":"10.1016/j.retram.2023.103389","DOIUrl":"10.1016/j.retram.2023.103389","url":null,"abstract":"<div><p>Immune thrombocytopenia is a common heterogeneous autoimmune disease that is characterized by decreasing peripheral blood platelet counts and increasing risk of bleeding. Studies have shown that an imbalance between T helper 17 (Th17) and Regulatory T (Treg) cells differentiated from CD4⁺T-cells is a key factor influencing the development and pathogenesis of immune thrombocytopenia. Th17 cells promote the development of chronic inflammatory disorders and induce autoimmune diseases, whereas Treg cells regulate immune homeostasis and prevent autoimmune diseases. Several regulators affecting the production and maintenance of these cells are also essential for proper regulation of Th17/Treg balance; these regulatory factors include cell surface proteins, miRNAs, and cytokine signaling. In this review, we focus on the function and role of balance between Th17 and Treg cells in immune thrombocytopenia, the regulatory factors, and therapeutic goals of this balance in immune thrombocytopenia.</p></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"71 2","pages":"Article 103389"},"PeriodicalIF":4.1,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9640751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Are we there yet? cellular therapies for cutaneous T cell lymphoma","authors":"Pinar Ataca Atilla ,&nbsp;Erden Atilla","doi":"10.1016/j.retram.2023.103390","DOIUrl":"10.1016/j.retram.2023.103390","url":null,"abstract":"<div><p><span><span>Cutaneous T cell<span><span> lymphomas (CTCLs) are a heterogenous group of skin-involved T-cell non-Hodgkin lymphoma which Mycosis Fungoides and </span>Sezary Syndrome<span> are the most common variants. Despite considerable progress in distinguishing the pathophysiology<span>, the treatment options are still limited for advanced-stage disease. Recent approval of novel agents such as </span></span></span></span>vorinostat<span>, brentuximab vedotin<span> and mogamulizumab paved a way. </span></span></span>Allogeneic hematopoietic stem cell transplantation has been shown to be a feasible option in selected advanced-stage CTCL patients. Chimeric antigen receptor (CAR) T cells have been promising for the treatment of B-cell tumors and have been approved for second-line treatment in non-Hodgkin's lymphoma. Although several obstacles still need to be addressed, CAR T cell treatment for CTCLs seems not far off. This review discusses new discoveries in pathophysiology, the state of cellular therapies in current practice, challenges for cellular treatment in advanced CTCL, and how to overcome these challenges.</p></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"71 2","pages":"Article 103390"},"PeriodicalIF":4.1,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9647176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}