Cytotherapy最新文献

{"title":"Cell and gene therapy approvals in Asia: regulatory landscape, access and affordability.","authors":"William Ying Khee Hwang, Sudipto Bari, Shin Kawamata, Bryan Choi, Chaiyong Koaykul, He Huang, Pawan Gupta","doi":"10.1016/j.jcyt.2025.08.005","DOIUrl":"https://doi.org/10.1016/j.jcyt.2025.08.005","url":null,"abstract":"<p><p>Cell and gene therapies (CGTs) are revolutionizing the treatment paradigm for a range of life-threatening and rare conditions, offering curative potential where conventional therapies have fallen short. In Asia, the CGT landscape has matured significantly in recent years, driven by regulatory reforms, increased local development and a growing number of product approvals. This updated review presents a comprehensive analysis of CGT regulatory frameworks, product approvals, pricing trends and reimbursement policies across six key Asian markets: Singapore, Japan, South Korea, China, India and Thailand. Drawing upon updated data from 2023 to 2025, we examine differences in regulatory maturity, access pathways, affordability and local manufacturing capabilities. The review highlights how certain countries, such as Japan and South Korea, have successfully implemented fast-track regulatory pathways, while others, like India and China, have emphasized domestic innovation to drive down costs. Despite progress, affordability, scalability and sustainable reimbursement remain persistent challenges. By presenting an up-to-date comparative analysis and synthesizing emerging policy innovations, this article offers insights into opportunities for harmonization, equitable access and future policy planning in Asia's rapidly evolving CGT sector.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and qualification of a sensitive method for residual feeder cell detection in NK cell therapy products.","authors":"Elizabeth Castro-Rivera, Alexandra Aquino-Acevedo, Li Chen, Myraida Toledo-Rojas, Kevin Avilés-Padilla, Daphne Ayala-Torres, Eliezer Romeu-Bonilla, Lei Zhang, Tania Rodriguez, Ivone Bruno","doi":"10.1016/j.jcyt.2025.08.002","DOIUrl":"https://doi.org/10.1016/j.jcyt.2025.08.002","url":null,"abstract":"<p><p>Cellular therapies must meet stringent regulatory standards for safety and quality. These requirements include the thorough evaluation of all manufacturing components, particularly residual cellular materials, and the potential impact of their presence in the final product. In this study we describe the development and qualification of a safety test method that supports the release of a Natural Killer (NK) cells drug product that is expanded by activation through a combination of cytokines and interaction with feeder cells, derived from a monoclonal K-562 cell line, modified to express 4-1BBL and mbIL-21 genes. In response to the safety and regulatory requirements with the use of feeder cells in NK cell manufacturing for clinical applications, and the limitation of current methodologies, we developed a residual test method enhanced by whole-genome sequencing and copy number analysis via droplet digital PCR (ddPCR). The method guarantees accurate identification of target cells via copy number with high specificity and precision with a coefficient of variation of <10%, linearity (R² = 0.999), and accuracy (72-115% recovery). The linear range reached a lower limit of quantification (LLOQ) of 0.1% and a lower limit of detection (LLOD) of 0.02%. These results support the applicability of this method for residual cell detection and release testing of cellular immunotherapies. Importantly, the methodological framework described here is broadly applicable and can be adapted for other cell therapy products where residual unwanted cells pose a risk of contamination in the final product, offering an adaptable, sensitive, and regulatory-compliant solution for safety testing.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PSCA-CAR-NK cells exert cytotoxic activity against PSCA-expressing tumor cells and are characterized by a specific chemokine profile.","authors":"Rodion A Velichinskii, Maria A Streltsova, Julia D Vavilova, Anna A Boyko, Tatyana N Belovezhets, Maria V Grechikhina, Elena I Kovalenko","doi":"10.1016/j.jcyt.2025.08.001","DOIUrl":"https://doi.org/10.1016/j.jcyt.2025.08.001","url":null,"abstract":"<p><p>Genetic modification of NK cells with chimeric antigen receptors (CARs) is a rapidly evolving approach to treating tumor diseases. CAR-NK technology is being developed for various antigens associated with both hematologic and solid tumors. In this study, peripheral blood NK cells overexpressing CAR against prostate stem cell antigen (PSCA) were obtained using retroviral transduction. To assess the specific functional activity of the PSCA-CAR-NK cells, we used cell lines modified to express surface PSCA via lentiviral transduction. The increased specific cytotoxic responses of PSCA-CAR-NK cells against these PSCA-positive cell lines were demonstrated using two alternative in vitro methods: a degranulation assay measuring CD107a expression level on the NK cell surface and a cytotoxicity test assessing fluorescent dye release from dying target cells. The specific cytotoxicity of PSCA-CAR-NK cells was confirmed using the BxPС-3 tumor cell line spontaneously expressing PSCA. In addition, profiles of chemokine receptors involved in the antitumor response, including CCR7, CXCR1, CXCR3 and CXCR4, were analyzed in NK cell subsets ex vivo, in IL-2/feeder cell-activated NK cells, and in transduced NK cells. We observed that the expression levels of CCR7 and CXCR4 on CD56⁺ NK cells and in the CD56⁺CD57⁺ fraction were highest in the activated state, decreasing after transduction. Proportion of NK cells expressing the CXCR1 receptor markedly decreased after activation while that of CXCR3 increased, the transduction procedure had no significant influence on the CXCR1 and CXCR3 levels. Following transduction, PSCA-CAR-NK cells showed increased levels of CCR7 expression compared to unmodified GFP-NK cells, most marked in more mature cells expressing CD57 or KIR2DL2/3. Moreover, an increased CXCR3 expression was noted in CD57⁺ subsets of the PSCA-CAR-NK cells. Since the ability of NK cells to migrate to lymph nodes and reach tumor sites depends on the presence of CCR7 and CXCR3 receptors, respectively, the patterns we have identified in the distribution of these chemokine receptors on cytotoxic PSCA-CAR-NK cells are particularly interesting and may be useful in the context of fighting solid tumors.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145056059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fast tumor-infiltrating lymphocytes (TILs): rapid manufacture of an adoptive cellular therapeutic from pleural infiltrating T cells for intrapleural administration.","authors":"Vera S Donnenberg, John Lister, Charlene L Briedenbaugh, Patrick L Wagner, David L Bartlett, Albert D Donnenberg","doi":"10.1016/j.jcyt.2025.06.011","DOIUrl":"https://doi.org/10.1016/j.jcyt.2025.06.011","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background aims: &lt;/strong&gt;Cancers of many different tissue origins can metastasize to the pleura, a space with a unique immune environment that predisposes to aggressive tumor behavior and the development of effusions, an exudative leakage of serous fluid accompanied by an immune infiltrate. Effusions are drained therapeutically to relieve dyspnea, often several times per week. Characteristically, they contain 50-1000 × 10&lt;sup&gt;6&lt;/sup&gt; viable pleural T cells (PITs), which can be reliably activated and expanded in culture, making them an ideal source for generation of a cellular therapeutic. We sought to determine the feasibility of a Good Manufacturing Practice-compliant, rapidly manufactured adoptive cellular therapeutic from pleural-infiltrating T cells and to determine the cytolytic activity against autologous tumor, cytokine secretion profile, and immune check point molecule (ICM) expression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Six products were generated from consecutively collected malignant pleural effusions (MPEs) drained from patients with breast (4) or non-small cell lung (2) cancer metastatic to the pleura. CD4+ and CD8+ cells were immunomagnetically selected, stimulated with anti-CD3/anti-CD28 and expanded in the presence of interleukin (IL)-7 and IL-15 (12.5 ng/mL each) using the Miltenyi CliniMACS Prodigy device. Cells were cultured for 8- 12 days. Cytokines were assayed in the MPE and in the culture medium before harvest using a multiplexed bead assay. Cytolytic activity of the final cellular product formulation against an autologous tumor was measured in a 4-hour killing assay by lactate dehydrogenase release. T-cell content, ICM expression and intracellular interferon ɣ were assessed by flow cytometry.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;All MPEs successfully generated products containing 0.7 to 3.2 × 10&lt;sup&gt;9&lt;/sup&gt; viable T cells. All final products showed no growth in bacterial or fungal cultures. T-cell purity was 98.3 ± 1.7% (mean, standard deviation), viability was 97.6 ± 1.7% and T-cell fold expansion was 14.3 ± 10.6. Twenty cytokines (excluding IL-7 and IL-15) were present in the culture supernatants at ≥10 pmol/L. These include granzyme B, interferon-ɣ, IL-13, perforin, granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-α. In the final cellular product formulation, 69 ± 28% of CD4+ T cells, and 75 ± 27% of CD8+ T-cells produced interferon-ɣ without additional stimulation. ICM expression was well correlated between CD4+ and CD8+ T cells and was relatively low, with TIGIT (44.6 ± 10.9%) and programmed cell death protein 1(21.1 ± 6.7%) being the highest. All products evidenced cytolytic activity against an autologous tumor, with maximal lysis ranging from 19.4% to 100% and cytolytic indices ranging from 4.3 to 21.1.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;We conclude that Fast tumor-infiltrating lymphocytes (Fast TIL), an adoptive cellular therapeutic generated from drained MPEs, can be rapidly and reli","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144977247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subscription information","authors":"","doi":"10.1016/S1465-3249(25)00795-9","DOIUrl":"10.1016/S1465-3249(25)00795-9","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 9","pages":"Page A5"},"PeriodicalIF":3.2,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144827636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aims and Scope","authors":"","doi":"10.1016/S1465-3249(25)00792-3","DOIUrl":"10.1016/S1465-3249(25)00792-3","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 9","pages":"Page A1"},"PeriodicalIF":3.2,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144827101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Very early recovery of T cells after alpha/beta T cell-depleted haploidentical HSCT predicts the outcome in children with leukemia.","authors":"Svetlana Glushkova, Larisa Shelikhova, Kirill Voronin, Maria Dunaikina, Sergey Blagov, Dmitriy Pershin, Viktoria Vedmedskaya, Maria Fadeeva, Susanna Arakelyan, Yakov Muzalevskii, Alexei Kazachenok, Yuliya Skvortsova, Dmitry Balashov, Alexei Maschan, Michael Maschan","doi":"10.1016/j.jcyt.2025.07.005","DOIUrl":"10.1016/j.jcyt.2025.07.005","url":null,"abstract":"<p><strong>Background: </strong>Functional immune reconstitution (IR) is a key factor in determining the success of hematopoietic stem cell transplantation (HSCT). IR depends on a number of factors and is typically delayed by ex vivo T cell depletion of the graft. αβ T cell depletion (αβ TCD) platform was reported to be associated with improved IR.</p><p><strong>Objective: </strong>In this retrospective study, we've focused on a homogeneous cohort of 262 children with acute leukemia first transplanted in complete remission, and investigate whether very early recovery of NK and T cells, as well as αβ and γδ T subsets, is associated with clinical outcomes.</p><p><strong>Study design: </strong>The grafts were obtained from apheresis products and processed by αβ TCD method. IR of lymphocyte subpopulations was measured in peripheral blood (PB) on day +30 after HSCT by flow cytometry.</p><p><strong>Results: </strong>The study suggests that in the early post-HSCT period, higher absolute number of T cells, despite being far below the normal range and having a rather limited T cell receptors repertoire, is associated with radically improved non-relapse mortality (NRM). Multivariate analysis confirmed the independent effect of T-cell IR on NRM. Our results show that each 10-fold increase in T cell PB count is associated with a 2.1-fold reduction in NRM (cause-specific Hazard Ratio (csHR) 0.47), independent from other important factors such as aGVHD or serotherapy use.</p><p><strong>Conclusion: </strong>Based on these results we suggest that T cells recovery on day +30 after HSCT can be used in predicting NRM risk in the setting of αβ TCD HSCT. Early intervention for IR improvement can be planned.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144977334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overcoming barriers to referral for CAR T-cell therapy in patients with non-Hodgkin aggressive B-cell lymphomas: A Delphi consensus.","authors":"Stefano Luminari, Annalisa Chiappella, Alice Di Rocco, Luca Arcaini, Roberto Freilone, Marco Ladetto, Massimo Martino, Pellegrino Musto, Luigi Rigacci, Carlo Visco, Paolo Corradini, Pier Luigi Zinzani","doi":"10.1016/j.jcyt.2025.07.007","DOIUrl":"https://doi.org/10.1016/j.jcyt.2025.07.007","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of aggressive B-cell non-Hodgkin lymphoma, particularly in relapsed/refractory large B-cell lymphoma and mantle cell lymphoma. Despite its transformative potential, significant challenges persist in optimizing patient identification and referral pathways to ensure timely and equitable access. This expert consensus, developed through the Delphi methodology, analyzes key barriers to the referral process and proposes structured solutions to enhance collaboration between referring treatment centers (RTCs) and qualified treatment centers (QTCs). Our findings highlight the importance of early and timely identification of CAR T-eligible patients through standardized disease assessments and strategies to streamline patient access through structured collaboration between RTCs and QTCs that can help overcome patient-specific logistical challenges. Proposed solutions should be broadly applicable across different health care systems. Addressing these clinical and logistical barriers in the referral process will be crucial for maximizing the benefits of CAR T-cell therapy and expanding its accessibility to a broader patient population.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subscription information","authors":"","doi":"10.1016/S1465-3249(25)00770-4","DOIUrl":"10.1016/S1465-3249(25)00770-4","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 8","pages":"Page A5"},"PeriodicalIF":3.7,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144712023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detailed analysis of the effects of a NOT gate on activation and growth of T cells.","authors":"Yuta Ando, Jingli A Zhang, Ethan A McLeod, Jon Torres, Dongwoo R Lee, Julyun Oh, Sanam Shafaattalab, Kelly C Radecki, Kathleen Cunningham, Aaron D Flynn, Nicolas Pedroncelli, Mark L Sandberg, Breanna DiAndreth, Alexandre Zampieri, Jason Wang, Talar Tokatlian, Lu Min Wong, Han Xu, Alexander Kamb","doi":"10.1016/j.jcyt.2025.06.014","DOIUrl":"https://doi.org/10.1016/j.jcyt.2025.06.014","url":null,"abstract":"<p><strong>Background aims: </strong>Dual-receptor NOT gates provide a mechanism to target effector cells to antigens that are absent in specific tissues, a situation that occurs frequently in cancer. For example, loss of heterozygosity (LOH) is a genetic event that removes large segments of one or the other homologous chromosome. Roughly 20% of the genes in an average solid tumor undergo LOH by the time of clonal neoplastic expansion, such that these irreversible genetic lesions are present in every cell of the tumor. To exploit this opportunity for selective targeting and other situations that arise in disease, a version of a NOT gate called Tmod^TM technology has been developed. The Tmod platform incorporates two receptors: an activator based on a CAR or TCR, and a blocker based on the LIR-1 inhibitory receptor.</p><p><strong>Methods: </strong>MHC class-I-regulated constructs display robust modularity, functioning well with a variety of activators-both CARs and TCRs-and blocker antigens encoded by different HLA class I alleles. We explore the details of activation, proliferation and cytotoxicity of the Tmod technology, focusing on a HER2 construct, but generalizing the conclusions by experiments with other Tmod constructs.</p><p><strong>Results: </strong>We show that Tmod cells exhibit potent, selective tumor-killing even when surrounded by class-I-expressing cells in 3-dimensional spheroids in vitro and in the mouse body. This behavior is largely ligand-dependent, though there are small ligand-independent effects which are mainly ascribed to mechanisms other than the ITIM sequences of the LIR-1 blocker.</p><p><strong>Conclusions: </strong>These detailed studies demonstrate that most of Tmod regulation is ligand dependent. Expression levels of the CAR affect activation/proliferation in a LIR-1 NOT gate, but the ITIM signaling module plays only a minor role in ligand-independent activity.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144977207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}