Moloud Ahmadi, Nicholas Putnam, Max Dotson, Danny Hayoun, Jasmine Padilla, Nujhat Fatima, Prajakta Bhanap, Gertrude Nonterah, Xavier de Mollerat du Jeu, Yongchang Ji
{"title":"Accelerating CAR T cell manufacturing with an automated next-day process","authors":"Moloud Ahmadi, Nicholas Putnam, Max Dotson, Danny Hayoun, Jasmine Padilla, Nujhat Fatima, Prajakta Bhanap, Gertrude Nonterah, Xavier de Mollerat du Jeu, Yongchang Ji","doi":"10.1016/j.retram.2024.103489","DOIUrl":"10.1016/j.retram.2024.103489","url":null,"abstract":"<div><div>The traditional method of CAR T cell production involves lengthy <em>ex-vivo</em> culture times which can result in the reduction of crucial naïve T cell subsets. Moreover, traditional CAR T cell therapy manufacturing processes can prolong time-to-patient, potentially delaying patient treatment, and contribute to disease progression. In this study, we describe an innovative and semi-automated 24-hour CAR T manufacturing process that yields a higher percentage of naïve/stem-cell like T cells which showed high cytotoxic activity and cytokine release in vitro. The data supports the feasibility of implementing this streamlined manufacturing process in clinics. This approach also has the potential to enhance CAR T therapy efficacy and improve patient access to therapy.</div></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"73 1","pages":"Article 103489"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873457","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":"Unraveling misinterpretations in pediatric COVID-19 admission trends: The Impact of CDC Reporting Changes","authors":"Yoshiyasu Takefuji","doi":"10.1016/j.retram.2024.103490","DOIUrl":"10.1016/j.retram.2024.103490","url":null,"abstract":"","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"73 1","pages":"Article 103490"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973286","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":"Thanks to reviewers","authors":"","doi":"10.1016/j.retram.2025.103507","DOIUrl":"10.1016/j.retram.2025.103507","url":null,"abstract":"","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"73 1","pages":"Article 103507"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610177","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}
Giorgia Battipaglia, Nicola Polverelli, Joe Tuffnell, Patrizia Chiusolo, Marie Robin, Massimiliano Gambella, Annoek Broers, Elisa Sala, Jakob Passweg, Sabine Furst, Lone Smidtrup Friis, Remy Dulery, Moniek de Witte, Micha Srour, Maria Chiara Finazzi, Claudia Wehr, Arnon Nagler, Deborah Richardson, Wolfgang Bethge, Andrew Clark, Joanna Drozd-Sokolowska, Kavita Raj, Tomasz Czerw, Juan Carlos Hernández-Boluda, Donal P McLornan
{"title":"Evaluation and management of hepatic dysfunction, portal hypertension and portal/splanchnic vein thrombosis in patients with myelofibrosis undergoing allogeneic haematopoietic cell transplantation: A practice based survey on behalf of the Chronic Malignancies Working Party of the EBMT.","authors":"Giorgia Battipaglia, Nicola Polverelli, Joe Tuffnell, Patrizia Chiusolo, Marie Robin, Massimiliano Gambella, Annoek Broers, Elisa Sala, Jakob Passweg, Sabine Furst, Lone Smidtrup Friis, Remy Dulery, Moniek de Witte, Micha Srour, Maria Chiara Finazzi, Claudia Wehr, Arnon Nagler, Deborah Richardson, Wolfgang Bethge, Andrew Clark, Joanna Drozd-Sokolowska, Kavita Raj, Tomasz Czerw, Juan Carlos Hernández-Boluda, Donal P McLornan","doi":"10.1016/j.retram.2024.103476","DOIUrl":"10.1016/j.retram.2024.103476","url":null,"abstract":"<p><p>Heterogeneous approaches exist in regard to the management of disease-related co-morbidities in potential allogeneic haematopoietic cell transplantation (allo-HCT) candidates with myelofibrosis (MF). The EBMT Chronic Malignancies Working Party launched an electronic survey to evaluate how MF-specific comorbidities are approached and whether they ultimately affect the decision to transplant. A total of 41/63 (65%) Centers, all of whom were experienced in the management of MF allo-HCT, responded. Responses were aggregated and reported in a comparative fashion. Screening for portal hypertension (PH) was routinely performed in 54% centers, never in 12% and guided by clinical manifestations in the remaining. Involvement of hepatologists/gastroenterologists was always/very often considered in patients with signs of PH prior to transplant. Centers reported that radiological evidence of PH did not routinely represent a formal contraindication for allo-HCT in most cases (78%). Of note, most centers (61%) did not perform routine screening for gastroesophageal varices; this was systematically considered or guided by clinical manifestations in only 7% and 32% centers, respectively. Presence of gastroesophageal varices was always (15%) or occasionally (19%) considered a formal contraindication to allo-HCT. A prior history of portal vein thrombosis never (78%) or occasionally (15%) represented a formal contraindication. Three Centers would not proceed to transplant in such cases. Less importance was assigned to non-portal splanchnic vein thrombosis (SVT), with all but one centre proceeding to transplant regardless of prior SVT. This survey highlights a considerable heterogeneity across responding centers in approaching MF-related comorbidities prior to transplant, suggesting that harmonisation guidelines are needed to address these issues in this patient population.</p>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"73 1","pages":"103476"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512931","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":"Optimizing CAR-T cell function in solid tumor microenvironment: insights from culture media additives","authors":"Wenwen Chen, Luxia Xu, Zhigang Guo, Muya Zhou","doi":"10.1016/j.retram.2024.103491","DOIUrl":"10.1016/j.retram.2024.103491","url":null,"abstract":"<div><div>Cancer remains one of the most pressing health challenges worldwide. Recently, chimeric antigen receptor (CAR)-T cell therapy has emerged as a promising approach for treating hematological cancers. However, the translation of CAR-T cell therapy to solid tumors faces formidable obstacles, notably the immunosuppressive tumor microenvironment. Within solid tumors, CAR-T cells encounter a hostile milieu that promotes exhaustion and diminishes their long-term effectiveness against cancer cells. Optimizing the manufacturing process is paramount to ensuring the efficacy of CAR-T cell therapy in solid tumors. A critical aspect of this optimization lies in refining the composition of cell culture media. By supplementing basic culture media with specific additives, researchers aim to improve the behavior and functionality of CAR-T cells, thereby enhancing their therapeutic potential. This review delves into the culture media additives that have been investigated or show promise in modulating CAR-T cell phenotypes and enhancing their anti-tumor efficacy. We explore various types of additives and their mechanisms of action to mitigate exhaustion and augment persistence within the challenging solid tumor microenvironment. By shedding light on the latest advancements in culture media optimization for CAR-T cell therapy, this review aims to provide insights into novel strategies for overcoming the hurdles posed by solid tumors. Ultimately, these insights hold the potential to enhance the effectiveness of CAR-T cell therapy and improve outcomes for cancer patients.</div></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"73 2","pages":"Article 103491"},"PeriodicalIF":3.2,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973290","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":"Sexual and emotional life among patients with hematological malignancy—Special concerns in low- and middle- income countries (LMICs)","authors":"Tamim Alsuliman , Paolo Musiu , Lugien AlAsadi , Ziad Aljarad , Zora Marjanovic , Amer Beitinjaneh , Réda Garidi","doi":"10.1016/j.retram.2024.103486","DOIUrl":"10.1016/j.retram.2024.103486","url":null,"abstract":"","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"73 1","pages":"Article 103486"},"PeriodicalIF":3.2,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142747473","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":"DNMT3A-related overgrowth syndrome presenting with immune thrombocytopenic purpura","authors":"Abdullah Sezer , Öznur Kaya Güneş , Burçak Kurucu","doi":"10.1016/j.retram.2024.103478","DOIUrl":"10.1016/j.retram.2024.103478","url":null,"abstract":"<div><div>Tatton-Brown-Rahman syndrome (TBRS) is characterized by overgrowth, cognitive deficiency, and distinctive facial features resulting from germline <em>DNMT3A</em> variants. This report describes a four-year-old female diagnosed with TBRS due to a de novo and novel heterozygous <em>DNMT3A</em> variant, NM_022552.5:c.1627G>C:p.(Gly543Arg). Alongside typical TBRS features, she had a history of hospitalization for immune thrombocytopenic purpura (ITP) at five months old. While ITP is clinically diagnosed and has multifactorial origins, studies have demonstrated its autoimmune and genetic components. DNMT3A protein, responsible for DNA methylation, regulates various cellular processes, including hematopoiesis and autoimmunity. It has been reported that ITP patients exhibit decreased expression of <em>DNMT3A</em>, and specific variants linked to decreased platelet counts have been identified in a murine model for TBRS. Additionally, some case reports have been described with multiple cytopenias and thrombocytopenia without hematologic malignancy. In conclusion, this report emphasizes for the first time the occurrence of ITP in a TBRS patient and suggests that autoimmune and hematologic disorders may need to be considered in the follow-up of these patients. However, further evidence is required to establish a direct correlation.</div></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"73 1","pages":"Article 103478"},"PeriodicalIF":3.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142696196","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}
Yifan Liu , Gangfeng Xiao , Yang Liu , Sanfang Tu , Bin Xue , Yadi Zhong , Cailu Zhang , Lili Zhou , Shiguang Ye , Yan Lu , Bing Xiu , Wenjun Zhang , Yi Ding , Jianfei Fu , Ping Li , Liang Huang , Xiu Luo , Aibin Liang
{"title":"CAR T-cell therapy combined with autologous hematopoietic cell transplantation in patients with refractory/relapsed Burkitt Lymphoma","authors":"Yifan Liu , Gangfeng Xiao , Yang Liu , Sanfang Tu , Bin Xue , Yadi Zhong , Cailu Zhang , Lili Zhou , Shiguang Ye , Yan Lu , Bing Xiu , Wenjun Zhang , Yi Ding , Jianfei Fu , Ping Li , Liang Huang , Xiu Luo , Aibin Liang","doi":"10.1016/j.retram.2024.103477","DOIUrl":"10.1016/j.retram.2024.103477","url":null,"abstract":"<div><div>Burkitt lymphoma (BL) is a highly aggressive type of non-Hodgkin lymphomas that have a high likelihood of relapse and are highly refractory to initial treatment. While high-intensity chemotherapy has improved the outcomes, many adult patients still experience treatment failure, and effective salvage therapies are limited. This study retrospectively analyzed the outcomes of 21 relapsed or refractory (R/R) adult BL patients treated with chimeric antigen receptor T-cell (CAR-T) therapy, combined or not with hematopoietic cell transplantation (HCT), across four Chinese hospitals. Patients were grouped based on treatment strategies: autologous HCT followed by CAR T-cell therapy (auto-HCT+CART group, <em>n</em> = 8), and CAR T-cell therapy alone (CART group, <em>n</em> = 13). The auto-HCT+CART group demonstrated superior outcomes, with an overall response rate (ORR) of 87.5 % and significantly higher 1-year overall survival (OS) and progression-free survival (PFS) rates compared to the CART group (<em>p</em> = 0.014 and <em>p</em> = 0.045, respectively). These findings suggest that combining auto-HCT with CAR-T therapy may enhance long-term disease control in R/R BL patients. These encouraging results highlight the need for further prospective studies to validate our data.</div></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"73 1","pages":"Article 103477"},"PeriodicalIF":3.2,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142551935","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}
Masoumeh Asadi , Ali Dalir Ghaffari , Fatemeh Mohammadhasani
{"title":"In silico analysis and structural vaccinology prediction of Toxoplasma gondii ROP41 gene via immunoinformatics methods as a vaccine candidate","authors":"Masoumeh Asadi , Ali Dalir Ghaffari , Fatemeh Mohammadhasani","doi":"10.1016/j.retram.2024.103475","DOIUrl":"10.1016/j.retram.2024.103475","url":null,"abstract":"<div><h3>Introduction</h3><div><em>Toxoplasma gondii</em> (<em>T. gondii</em>) infects all warm-blooded animals, including humans. Currently, no effective treatments exist to prevent the generation of chronic tissue cysts in infected hosts. Therefore, developing a vaccine to protect to deal with toxoplasmosis is a promising strategy, as a single immunization could provide lifelong protective immunity. Rhoptry proteins (ROPs) play a vital role for the parasite's survival within host cells and perform critical functions during different phases of parasite invasion. Little is known about ROP41 gene. Nevertheless, Understanding the characteristics of ROP41 will enhance diagnostic and vaccine research.</div></div><div><h3>Materials and Methods</h3><div>The current article provides a comprehensive analysis of the essential components of the ROP41 protein, including its transmembrane domain, physico-chemical properties, subcellular location, tertiary and secondary structures, and potential T- and B-cell epitopes. These features were determined by many bioinformatics approaches to identify possible epitopes for developing a highly effective vaccine.</div></div><div><h3>Results</h3><div>ROP41 protein showed 36 possible post-translational modification regions. The ROP41 protein secondary structure contains 17.35 % extended strand, 33.47 % alpha-helix, and 49.18 % random coil. Also, ROP41 showed many possible B- and T-cell epitopes. According to the Ramachandran plot, 90.78 % of amino acid residues had been placed in favored, 3.28 % in outlier, and 5.94 % in allowed areas. Also, the allergenicity and antigenicity evaluation indicated that ROP41 is non-allergenic and immunogenic.</div></div><div><h3>Conclusion</h3><div>The current study offered critical basic and conceptual information on ROP41 to increase a successful vaccine in opposition to continual and acute toxoplasmosis for in addition in vivo assessments. Further research is necessary for the development of vaccines utilizing ROP41 alone or combined with various antigens.</div></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"73 1","pages":"Article 103475"},"PeriodicalIF":3.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512932","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":"Effect and safety of recombinant human thrombopoietin on haematopoietic reconstitution after allogeneic haematopoietic cell transplantation","authors":"Meilin Tian , Le Ma , Jieping Chen , Qiang Gong","doi":"10.1016/j.retram.2024.103472","DOIUrl":"10.1016/j.retram.2024.103472","url":null,"abstract":"<div><div>Delayed platelet engraftment (DPE) and thrombocytopenia are common complications following myeloablative conditioning in the advanced stage of allogeneic haematopoietic cell transplantation (allo-HCT), and they are associated with transplantation-related mortality and poor prognosis. Therefore, promoting haematopoietic reconstitution after allo-HCT plays a key role in improving patient outcomes. The aim of this retrospective study was to assess the effectiveness and safety of recombinant human thrombopoietin (rhTPO) in promoting haematopoietic reconstruction after allo-HCT. The study included 210 patients who underwent transplantation, with 158 in the rhTPO group and 52 in the control group. Of the total patient population, 120 were males and 90 were females, with a median age of 31 years (range=6 to 59 years). The results showed that the rhTPO group had a median platelet engraftment time that was 14.1 days shorter than that of the control group (14.1 days vs. 21.9 days; <em>P</em> < 0.001). The time for platelet count recovery to 50 × 10^9/L was also shorter in the rhTPO group than in the control group (21.7 days vs. 30.3 days; <em>P</em> < 0.001). Additionally, the granulocyte engraftment time was shorter in the rhTPO group (14.3 days vs. 18.2 days; <em>P</em> < 0.001). There was no significant difference in overall survival (OS) between the rhTPO group and the control group at 2 years after transplantation (77.2% vs. 65.4 %; <em>P</em> = 0.08). Furthermore, there were no significant differences in the amount of platelet transfusions, the rate of platelet engraftment, the rate of DPE, or the incidence of Grade 4 haemorrhage between the groups. Moreover, no adverse reactions were found in the rhTPO group. This study demonstrated that rhTPO administration after allo-HCT effectively reduced the time required for platelet and granulocyte engraftment and was safe.</div></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"73 1","pages":"Article 103472"},"PeriodicalIF":3.2,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378611","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}