EJC paediatric oncology最新文献

{"title":"Japan’s contribution to an ongoing global pediatric cancer clinical trial: The experience of the National Cancer Center Hospital (NCCH) in Tokyo","authors":"Miho Nakajima,&nbsp;Ayumu Arakawa,&nbsp;Chitose Ogawa","doi":"10.1016/j.ejcped.2024.100157","DOIUrl":"https://doi.org/10.1016/j.ejcped.2024.100157","url":null,"abstract":"<div><p>Compared to Europe and the United States, where the development of pediatric oncology drugs is mandated by law, Japan hosts fewer clinical trials. This can lead to a significant drug lag, especially in the case of treatments for pediatric solid tumors. Notably, regulatory authorities and the government have initiated discussions on strategies to mitigate Japan’s drug lag problem in pediatric oncology. Over the past decade, we have actively sought opportunities to participate in international collaborative clinical trials through Japan’s involvement in ACCELERATE and its predecessor organizations. This approach has aimed to address the issue above, coinciding with the ongoing centralization of medical care and advancements in genomic medicine, among other systems that support pediatric cancer care in Japan. Inspired by the ACCELERATE initiatives and in response to patient advocacy groups’ requests for new pediatric oncology drugs, Japan established its inaugural pediatric oncology support platform in 2021, the National Childhood Cancer Consortium (N3C). N3C comprises patient advocacy groups, industries, and academia. This work outlines the current status of pediatric drug development in Japan and highlights the initial successful experience of NCCH’s participation in a global clinical trial through ACCELERATE resulting in rapid preparation and patient recruitment. Participation of Asian countries including Japan in global collaborative clinical trials may benefit both pharmaceutical companies and the participating countries partnering to advance the development of pediatric oncology drugs.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000163/pdfft?md5=2f7099c73d2c72937b2ee48f61f1ec60&pid=1-s2.0-S2772610X24000163-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140161006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Telomere maintenance mechanisms in neuroblastoma: New insights and translational implications","authors":"Lisa Werr ,&nbsp;Carolina Rosswog ,&nbsp;Christoph Bartenhagen ,&nbsp;Sally L. George ,&nbsp;Matthias Fischer","doi":"10.1016/j.ejcped.2024.100156","DOIUrl":"https://doi.org/10.1016/j.ejcped.2024.100156","url":null,"abstract":"<div><p>The clinical behaviour of neuroblastoma ranges from spontaneous tumour regression or maturation into benign ganglioneuroma to fatal progression despite intensive treatment [1,2]. The mechanisms underlying the distinct phenotypes have remained uncertain yet. A number of recent studies noticed that activation of telomere maintenance mechanisms (TMM) in the malignant neuroblasts is strongly associated with high-risk disease and poor outcome, whereas TMM are absent in spontaneously regressing low-risk tumours, suggesting that telomere maintenance is essential to drive neuroblasts into the fully malignant state. Stabilization of the telomeres above a critical threshold is essential for cancer cells to gain replicative immortality and has thus been considered a hallmark of cancer [3]. In most high-risk neuroblastomas, TMM is conferred by induction of telomerase, either through genomic rearrangements of the <em>TERT</em> locus, encoding for the catalytic subunit of telomerase, or amplification of the <em>MYCN</em> proto-oncogene, whereas the alternative lengthening of telomeres (ALT) pathway is activated in approximately one-quarter of high-risk tumours [4–8]. We here review recent advances on our understanding of the mechanistic role of telomere maintenance in neuroblastoma pathogenesis, and discuss potential implications on neuroblastoma risk assessment and on the development of novel therapies directed against TMM.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000151/pdfft?md5=de1f29ad7bc35889849f4f9efb14f365&pid=1-s2.0-S2772610X24000151-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140138799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of childhood cancer survivors in Europe: a scoping review","authors":"Neimar de Paula Silva ,&nbsp;Andrea Gini ,&nbsp;Anastasia Dolya ,&nbsp;Murielle Colombet ,&nbsp;Isabelle Soerjomataram ,&nbsp;Danny Youlden ,&nbsp;Charles Stiller ,&nbsp;Eva Steliarova-Foucher ,&nbsp;the CRICCS consortium,&nbsp;Joanne Aitken ,&nbsp;Freddie Bray ,&nbsp;Murielle Colombet ,&nbsp;Neimar de Paula Silva ,&nbsp;Anastasia Dolya ,&nbsp;Friederike Erdmann ,&nbsp;Jeanette Falck Winther ,&nbsp;Andrea Gini ,&nbsp;Delphine Heenen ,&nbsp;Lars Hjorth ,&nbsp;Claudia E. Kuehni ,&nbsp;Danny Youlden","doi":"10.1016/j.ejcped.2024.100155","DOIUrl":"https://doi.org/10.1016/j.ejcped.2024.100155","url":null,"abstract":"<div><p>Childhood cancer survivors (CCS) require specialized follow-up throughout their lifespan to prevent or manage late effects of cancer treatment. Knowing the size and structure of the population of CCS is crucial to plan interventions. In this scoping review we reviewed studies that reported prevalence of CCS in Europe. We searched Medline, Web of Science, and Embase using permutations of terms referring to childhood, cancer, survivors, prevalence, registries, and Europe. We followed PRISMA-ScR guidelines to select studies and The Joanna Briggs Institute Prevalence Critical Appraisal Tool to evaluate their quality. From 979 unique studies published between 1989 and 2022, 12 were included. Limited-duration prevalence (LDP) for all childhood cancers, assessed in three studies using counting method, varied between 450 and 1240 persons per million. Complete prevalence (CP) of survivors of any childhood cancer except skin carcinomas, reported in three studies using observed data complemented with modelled data for the unobserved period, varied between 730 and 1110 persons per million. CP of survivors of an embryonal tumour was estimated by completeness index method in six studies. In four of them CP ranged from 48 to 95 persons per million for all embryonal tumours, while CP for those occurring in central nervous system was 43 per million in one study and CP for rhabdomyosarcoma was 17 per million in another. Information on prevalence of CCS in Europe is fragmented and inconsistent. The large variations in LDP and CP estimates were linked to differences in data availability, the selection of populations, prevalence measure, statistical method, incidence period, index date, age at diagnosis and prevalence, cancer types, sex, and, for LDP, also the length of follow-up. Standardisation of methodology and reporting are needed to systematically monitor and compare CCS prevalence in Europe and provide data to help address survivors’ needs.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X2400014X/pdfft?md5=4115c91bca18701bb5c80c478a2fce0c&pid=1-s2.0-S2772610X2400014X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140138798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Twinning to reduce research and innovation inequalities in paediatric solid tumours across Europe","authors":"Jelena Rascon ,&nbsp;Renata Blackute ,&nbsp;Alma Cerkauskiene ,&nbsp;Sabine Taschner-Mandl ,&nbsp;Nuno Andrade ,&nbsp;Adriana Planinic ,&nbsp;Stefan Rutkowski ,&nbsp;Ulrich Schuller ,&nbsp;Karsten Nysom ,&nbsp;Ruta Tuckuviene ,&nbsp;Jesper Brok ,&nbsp;Kjeld Schmiegelow ,&nbsp;Marry M. van den Heuvel-Eibrink ,&nbsp;M.E. Madeleine van der Perk ,&nbsp;Riccardo Haupt ,&nbsp;Monica Muraca ,&nbsp;Davide Saraceno ,&nbsp;Birgit Geoerger ,&nbsp;Giorgia Manuzi ,&nbsp;Ruth Ladenstein","doi":"10.1016/j.ejcped.2024.100153","DOIUrl":"https://doi.org/10.1016/j.ejcped.2024.100153","url":null,"abstract":"<div><p>Inequalities in research and innovations affect childhood cancer survival across Europe. Vilnius University Hospital Santaros Klinikos (VULSK, the coordinator) and eight research-intensive institutions from seven European countries implemented the TREL project (Twinning in Research and Education to improve survival in childhood solid tumours in Lithuania) supported by the Horizon 2020 Widening programme. TREL aimed to enhance translational, clinical, and survivorship research in paediatric CNS, neuroblastoma, and renal tumours to improve future treatment outcomes in Lithuania. From January 2021 to December 2023, 49 VULSK professionals and 55 peers from partner institutions collaborated in this twinning program. Achievements after three years were: nine educational events, the initiation of basic and clinical research on fertility preservation, ten VULSK researchers joining international research groups, six signed agreements to participate in international academic clinical trials and the implementation of the European Survivorship Passport. Thirty patients received individual treatment recommendations following multidisciplinary discussions with experts from partner institutions. Twenty-five rare genetic variants were classified by the twinning bioinformatician teams with direct consequences on patient management. In conclusion, coordination of the Horizon 2020 project enhanced VULKS’s research capacities, networking channels and attractiveness for industry and academia-initiated innovative actions that will improve survival rates in the long run.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000126/pdfft?md5=c32781086be65a384542762fae4be4dc&pid=1-s2.0-S2772610X24000126-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140031155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"131-I-MIBG therapy in combination with PARP inhibitors for young adult patient with relapsed neuroblastoma and DNA repair pathway alterations","authors":"Sarah Cohen-Gogo ,&nbsp;Amer Shammas ,&nbsp;Adam Shlien ,&nbsp;Meredith Irwin ,&nbsp;Daniel Morgenstern","doi":"10.1016/j.ejcped.2024.100152","DOIUrl":"https://doi.org/10.1016/j.ejcped.2024.100152","url":null,"abstract":"","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000114/pdfft?md5=d13c8be54bd68674569537c0f8ff2605&pid=1-s2.0-S2772610X24000114-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140016033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Malignant extracranial germ cell tumors in the Netherlands between 1990 and 2018: Stable incidence and improved survival","authors":"Caroline C.C. Hulsker ,&nbsp;Maya Schulpen ,&nbsp;Annelies M.C. Mavinkurve-Groothuis ,&nbsp;Otto Visser ,&nbsp;József Zsiros ,&nbsp;Marc H.W. Wijnen ,&nbsp;Ronald R. de Krijger ,&nbsp;Annette H. Bruggink ,&nbsp;Leendert H.J. Looijenga ,&nbsp;Henrike E. Karim-Kos ,&nbsp;Alida F.W. van der Steeg","doi":"10.1016/j.ejcped.2024.100148","DOIUrl":"https://doi.org/10.1016/j.ejcped.2024.100148","url":null,"abstract":"<div><h3>Background</h3><p>Population-based studies assessing long-term patterns of incidence and disease characteristics of germ cell tumors (GCTs) in children are scarce. We investigated incidence and survival trends of malignant extracranial GCTs in children using population-based nationwide data from the Netherlands.</p></div><div><h3>Methods</h3><p>All malignant extracranial GCTs diagnosed in patients aged 0–18 years between 1990 and 2018 were selected from the Netherlands Cancer Registry. Incidence rates were calculated as the average annual number of cases per 1 million person-years. Five-year overall survival (OS) was calculated.</p></div><div><h3>Results</h3><p>A total of 815 cases were identified. Gonadal GCTs (n=665, testis n=485, ovarian n=180) were more common than extragonadal GCTs (n=149). Stage distribution for testicular and extragonadal GCTs shifted between 1990 and 2004 and 2005–2018 towards more localized disease. The overall incidence remained stable over time, but a significant increase was noted for extragonadal GCTs in the 0–9 years age group. Survival of extragonadal GCTs (5-year OS 84.1%, 95% CI 77.1–89.1), in particular mediastinal GCTs (5-year OS 66.7%, 95% CI 45.7–81.1), was lower than that of gonadal GCTs (5-year OS testis 95.0%, 95% CI 92.7–96.7;ovary 97.8%, 95% CI 94.2–99.2). The 5-year OS of our entire cohort was 93.6% (95% CI 91.7–95.1). Five-year OS significantly increased from 89.5% (95% CI 86.1–92.2) in 1990–2004–97.4% (95% CI 95.3–98.5) in 2005–2018.</p></div><div><h3>Conclusions</h3><p>Although the incidence of all malignant pediatric extracranial GCTs remained stable during 1990–2018, an increase was observed for extragonadal GCTs in younger children (0–9 years). There was a shift towards more localized disease for testicular and extragonadal GCTs. Five-year OS increased over time exceeding 90% (91.4%, 95% CI 82.7–95.8) in the most recent diagnostic period. Mediastinal GCTs had the lowest OS, supporting the need for future research.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000072/pdfft?md5=503469431d7200fe24642a6af61277f3&pid=1-s2.0-S2772610X24000072-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139999308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How we approach early phase clinical trial and off-label therapy consults in pediatric oncology: The New Agents and Innovative Therapy (NAIT) team experience","authors":"Gabriel Revon-Rivière,&nbsp;Pauline Tibout,&nbsp;Jennifer Cabral,&nbsp;Aiman Siddiqi,&nbsp;Ashley Doka,&nbsp;Denise Mills,&nbsp;Karen Fung,&nbsp;Sandra Judd,&nbsp;Daniel A. Morgenstern,&nbsp;Sarah Cohen-Gogo","doi":"10.1016/j.ejcped.2024.100154","DOIUrl":"https://doi.org/10.1016/j.ejcped.2024.100154","url":null,"abstract":"<div><p>In the context of hard-to-cure disease, pediatric oncologists may have to explore novel therapy options and explain their rationale, risks and constraints to patients and caregivers. The New Agents and Innovative Therapy (NAIT) program at Hospital for Sick Children in Toronto facilitates patient enrollment in clinical trials as well as access to innovative therapies outside of clinical trials. Here, we summarize our experience with helping patients, caregivers, and their primary oncology team navigate information and access to new therapeutic options through enrollment in clinical trials but also off-label and compassionate use. We expose our approach to exploring clinical trial and other therapy options. We share lessons learned from clinical practice regarding the specific role of NAIT consultant, as opposed to the primary oncologist or the disease expert. We expand on ways to communicate regarding the objectives of early phase clinical trials, their methods and the important commitment asked from participants. We describe our views on equipoise, uncertainty and hope in this very specific practice. We support a model of shared decision making and empowerment of patients and caregivers. We also detail the use, benefits and challenges of virtual care applied to NAIT consults. Overall, we hope to contribute and facilitate the NAIT practice not only for trained trialists but also less-specialized teams.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000138/pdfft?md5=a358b55bee4d9dda2b38d12d51888a4b&pid=1-s2.0-S2772610X24000138-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140016032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emergent and underexplored oncolytic viruses for treating pediatric central nervous system tumors","authors":"Isabela Granha ,&nbsp;Gustavo Sartorelli ,&nbsp;Oswaldo Keith Okamoto ,&nbsp;Elisa Helena Farias Jandrey","doi":"10.1016/j.ejcped.2024.100151","DOIUrl":"https://doi.org/10.1016/j.ejcped.2024.100151","url":null,"abstract":"<div><p>High-grade pediatric Central Nervous System (CNS) tumors are frequent, highly aggressive, and the most common cause of cancer-associated death in children. Due to their unique features, such as heterogeneous tumor molecular characteristics, distinct microenvironment, challenging anatomical localization and the presence of the blood brain barrier, brain tumors are especially difficult to treat and often present a poor response to standard therapies (surgery, radio and chemotherapy). Because of that, there is a need for investigating more effective therapeutic approaches and, within this context, Oncolytic Viruses (OVs) have emerged as a promising new class of immunotherapeutic agents. These viruses have a natural or artificial tropism for cancer cells and their central mechanism of action is the direct oncolytic effect followed by activation of the immune response. As a consequence, the OV therapy can be safer than traditional approaches, and its use may help overcome some pediatric CNS tumor treatment challenges. In this review, we initially examine the potential therapeutic advantages that are intrinsically related to OVs infection mechanism. Then, we address the surpassing resistance mechanisms of available treatments for pediatric brain tumors and present some challenges to be taken into consideration in clinical application. We next provide an overview of preclinical studies focusing on the mechanisms of infection and also <em>in vitro</em> and <em>in vivo</em> findings of emergent and underexplored OVs, namely Zika virus, Measles virus, Reovirus, Poliovirus, Seneca Valley virus, Vaccinia virus, Myxoma virus and Parvovirus. Finally, we summarize the latest clinical trials using these underexplored OVs against pediatric solid tumors.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000102/pdfft?md5=6bcf2b90582bd93a2e40bf7c254884c3&pid=1-s2.0-S2772610X24000102-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139998919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAR T-cells for T-cell acute lymphoblastic leukemia","authors":"Marie Emilie Dourthe ,&nbsp;André Baruchel","doi":"10.1016/j.ejcped.2024.100150","DOIUrl":"https://doi.org/10.1016/j.ejcped.2024.100150","url":null,"abstract":"<div><p>T-cell acute lymphoblastic leukemia (T-ALL) has a dismal prognosis in case of relapsed or refractory disease. Contrary to B-ALL, few immunotherapies are available for T-ALL. Use of autologous CAR T-cells is challenging due to shared antigen between leukemic and normal T-cells responsible for fratricide and T-cell aplasia in case of persistence of CAR T-cells. Moreover, risk of contamination of the apheresis product by lymphoblasts remains an issue. To counteract these challenges several methods are used to edit T-cell such as protein expression blocker, CRISPR/Cas9 and base-editing. Other possibility is to use autologous T-cells naturally selected <em>in vitro</em> or donor-derived T-cells allowing gene edition and reduction of the risk of graft vs host disease. Encouraging results are obtained in preclinical and clinical studies for early response rate but several questions remain. Is the persistence of these cells requiring for maintaining the remission? Is it feasible to recover a target-negative T-cell population without risk of profound immunosuppression? Has an allogeneic stem cell transplantation to be planned for patients after CAR T-cells infusion? What about the risk of engineered T-cells in the long term?</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000096/pdfft?md5=43b91a189526444cfcf248b29b55d17c&pid=1-s2.0-S2772610X24000096-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139936597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome editing approaches for universal chimeric antigen receptor T cells","authors":"Avijeet Kumar Mishra,&nbsp;Waseem Qasim","doi":"10.1016/j.ejcped.2024.100149","DOIUrl":"https://doi.org/10.1016/j.ejcped.2024.100149","url":null,"abstract":"<div><p>Autologous chimeric antigen receptor (CAR) T cell therapy has revolutionised the management of certain B-cell malignancies. However, as bespoke therapies, challenges include complex manufacturing logistics and risks ranging from suboptimal harvests to inadvertent transduction and masking of blast populations. Premanufactured, ready -to -use allogeneic CAR T cells could mitigate some of these hurdles if barriers created by HLA (Human leukocyte antigen) mismatching can be addressed. Genome editing to disrupt TCRαβ (T-cell receptor αβ) expression has been shown to be effective in addressing alloreactivity and avoiding graft versus host disease (GVHD). Platforms including transcription activator-like effector nucleases (TALENs), homing endonucleases and clustered regularly interspersed short palindromic repeats (CRISPR) / Cas9 have allowed multiplex editing of TCR genes in combination with CD52, the target antigen of alemtuzumab, as a strategy to evade lymphodepletion used to prevent host v graft rejection effects. Alternative approaches have targeted pathways to prevent HLA expression on donor T cells, and have also allowed targeted insertion of CAR genes, including placing transgene expression under the control of endogenous transcriptional machinery. These tools have rapidly progressed to clinical trials, and applications have extended beyond B-cell malignancies, showing promising early results in other settings, including relapsed/refractory(r/r) T-cell leukaemia. Short term immunological effects and toxicities have been generally manageable, and long-term monitoring is ongoing to help build confidence in safety over time.</p></div>","PeriodicalId":94314,"journal":{"name":"EJC paediatric oncology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772610X24000084/pdfft?md5=009b31ff0c5884814369171601da3f60&pid=1-s2.0-S2772610X24000084-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139986335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}