Cytotherapy最新文献

{"title":"Cell and gene therapy investment: evolution and future outlook on investor perspectives","authors":"Maximiliano Kunze-Küllmer ,&nbsp;Asthika Goonewardene ,&nbsp;Sven Kili ,&nbsp;Stefanos Theoharis ,&nbsp;Patrick Rivers","doi":"10.1016/j.jcyt.2024.02.017","DOIUrl":"10.1016/j.jcyt.2024.02.017","url":null,"abstract":"<div><h3>Background aims</h3><p>To better understand the attitudes and behaviors of investors involved in funding cell and gene therapy (CGT) businesses, the Business Development and Finance) subcommittee of International Society for Cell and Gene Therapy, in collaboration with Truist Securities, conducted a broad survey of the investment community in late 2021.</p></div><div><h3>Methods</h3><p>This survey follows a similar study that this group executed in 2018, and the longitudinal comparisons between the two time periods provide insights into how investor behavior in the CGT field has evolved.</p></div><div><h3>Results</h3><p>The vast majority of investor respondents are specialist biotech investors who are primarily active in deploying capital in North America and Europe. There was a notable increase in the proportion of investors actively deploying capital in China and Japan between 2018 and 2021. The percentage of respondents’ portfolios dedicated to CGT companies has also increased in this period, reflecting a noteworthy trend in the therapeutic landscape.</p></div><div><h3>Conclusions</h3><p>Clinically significant data remain the dominant force behind investment decisions, whereas competition from other drug modalities has now emerged as the most-cited barrier to making a CGT investment, eclipsing safety concerns as the most significant barrier to investment in 2018. Concerns around manufacturing and scale-up have also increased in prominence amongst the investment community. Gene-editing technologies are attracting investors as the most compelling new CGT technology. This survey also revealed that most investors expect to increase their level of investment in allogeneic technologies relative to autologous products in the coming years.</p></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1465324924000641/pdfft?md5=5bc2661806c96f3dae28633c32c24048&pid=1-s2.0-S1465324924000641-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140121301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protocol improvement and multisite validation of a digital soft agar colony formation assay for tumorigenic transformed cells intermingled in cell therapy products","authors":"Kiyoko Bando ,&nbsp;Shinji Kusakawa ,&nbsp;Hideki Adachi ,&nbsp;Mika Yamamoto ,&nbsp;Miki Iwata ,&nbsp;Atsushi Kitanaka ,&nbsp;Eiichiro Ogimura ,&nbsp;Tomoharu Osada ,&nbsp;Maya Tamura ,&nbsp;Orie Terai ,&nbsp;Takeshi Watanabe ,&nbsp;Tomomi Yoda ,&nbsp;Takafumi Yotsumoto ,&nbsp;Kinuko Zaizen ,&nbsp;Yoji Sato","doi":"10.1016/j.jcyt.2024.03.005","DOIUrl":"10.1016/j.jcyt.2024.03.005","url":null,"abstract":"<div><h3>Background aims</h3><p>The administration of human cell-processed therapeutic products (hCTPs) is associated with a risk of tumorigenesis due to the transformed cellular contaminants. To mitigate this risk, these impurities should be detected using sensitive and validated assays. The digital soft agar colony formation (D-SAC) assay is an ultrasensitive <em>in vitro</em> test for detecting tumorigenic transformed cells in hCTPs. <em>Methods</em>: In this study, we first evaluated the colony formation efficiency (CFE) precision of tumorigenic reference cells in positive control samples according to a previously reported D-SAC assay protocol (Protocol I) from multiple laboratories. However, the CFE varied widely among laboratories. Thus, we improved and optimized the test protocol as Protocol II to reduce variability in the CFE of tumorigenic reference cells. Subsequently, the improved protocol was validated at multiple sites. Human mesenchymal stromal cells (hMSCs) were used as model cells, and positive control samples were prepared by spiking them with HeLa cells. <em>Results:</em> Based on the previously reported protocol, the CFE was estimated using an ultra-low concentration (0.0001%) of positive control samples in multiple plates. Next, we improved the protocol to reduce the CFE variability. Based on the CFE results, we estimated the sample size as the number of wells (Protocol II) and assessed the detectability of 0.0001% HeLa cells in hMSCs to validate the protocol at multiple sites. Using Protocol I yielded low CFEs (mean: 30%) and high variability between laboratories (reproducibility coefficient of variance [CV]: 72%). In contrast, Protocol II, which incorporated a relatively high concentration (0.002%) of HeLa cells in the positive control samples, resulted in higher CFE values (mean: 63%) and lower variability (reproducibility CV: 18%). Moreover, the sample sizes for testing were estimated as the number of wells per laboratory (314–570 wells) based on the laboratory-specific CFE (42–76%). Under these conditions, all laboratories achieved a detection limit of 0.0001% HeLa cells in hMSCs in a predetermined number of wells. Moreover, colony formation was not observed in the wells seeded with hMSCs alone.</p></div><div><h3>Conclusions</h3><p>The D-SAC assay is a highly sensitive and robust test for detecting malignant cells as impurities in hCTPs. In addition, optimal assay conditions were established to test tumorigenic impurities in hCTPs with high sensitivity and an arbitrary false negative rate.</p></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S146532492400094X/pdfft?md5=fe416cd0a77bedfcaf78ee9cd6d7932a&pid=1-s2.0-S146532492400094X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140150318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAR-T cell expansion platforms yield distinct T cell differentiation states","authors":"Hannah W. Song ,&nbsp;Michaela Prochazkova ,&nbsp;Lipei Shao ,&nbsp;Roshini Traynor ,&nbsp;Sarah Underwood ,&nbsp;Mary Black ,&nbsp;Vicki Fellowes ,&nbsp;Rongye Shi ,&nbsp;Marie Pouzolles ,&nbsp;Hsien-Chao Chou ,&nbsp;Adam T. Cheuk ,&nbsp;Naomi Taylor ,&nbsp;Ping Jin ,&nbsp;Robert P. Somerville ,&nbsp;David F. Stroncek ,&nbsp;Javed Khan ,&nbsp;Steven L. Highfill","doi":"10.1016/j.jcyt.2024.03.003","DOIUrl":"10.1016/j.jcyt.2024.03.003","url":null,"abstract":"<div><p>With investigators looking to expand engineered T cell therapies such as CAR-T to new tumor targets and patient populations, a variety of cell manufacturing platforms have been developed to scale manufacturing capacity using closed and/or automated systems. Such platforms are particularly useful for solid tumor targets, which typically require higher CAR-T cell doses. Although T cell phenotype and function are key attributes that often correlate with therapeutic efficacy, how manufacturing platforms influence the final CAR-T cell product is currently unknown. We compared 4 commonly used T cell manufacturing platforms (CliniMACS Prodigy, Xuri W25 rocking platform, G-Rex gas-permeable bioreactor, static bag culture) using identical media, stimulation, culture length, and donor starting material. Selected CD4⁺CD8⁺ cells were transduced with lentiviral vector incorporating a CAR targeting FGFR4, a promising target for pediatric sarcoma. We observed significant differences in overall expansion over the 14-day culture; bag cultures had the highest capacity for expansion while the Prodigy had the lowest (481-fold versus 84-fold, respectively). Strikingly, we also observed considerable differences in the phenotype of the final product, with the Prodigy significantly enriched for CCR7⁺CD45RA⁺ naïve/stem central memory (T_n/scm)-like cells at 46% compared to bag and G-Rex with 16% and 13%, respectively. Gene expression analysis also showed that Prodigy CAR-Ts are more naïve, less cytotoxic and less exhausted than bag, G-Rex, and Xuri CAR-Ts, and pointed to differences in cell metabolism that were confirmed via metabolic assays. We hypothesized that dissolved oxygen level, which decreased substantially during the final 3 days of the Prodigy culture, may contribute to the observed differences in T cell phenotype. By culturing bag and G-Rex cultures in 1% O₂ from day 5 onward, we could generate &gt;60% T_n/scm-like cells, with longer time in hypoxia correlating with a higher percentage of T_n/scm-like cells. Intriguingly, our results suggest that oxygenation is responsible, at least in part, for observed differences in T cell phenotype among bioreactors and suggest hypoxic culture as a potential strategy prevent T cell differentiation during expansion. Ultimately, our study demonstrates that selection of bioreactor system may have profound effects not only on the capacity for expansion, but also on the differentiation state of the resulting CAR-T cells.</p></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1465324924000914/pdfft?md5=6e3d790b444f0c12e79599de854b90aa&pid=1-s2.0-S1465324924000914-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140150406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new breakthrough in genome editing: the story of Casgevy","authors":"Beatriz Olalla, Paula Río","doi":"10.1016/j.jcyt.2024.06.003","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.06.003","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141405977","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":"PRESERVING CLINICAL EFFICACY OF MESENCHYMAL STEM CELLS WITH GLYCOSAMINOGLYCAN ADDITIVES","authors":"A. Shokoohmand, A. Srinivasan, L. Ling, F. R. D. O. Silva, M. Eio, X. Lu, M. Loberas, K. Tao, C. Tan, V. Nurcombe, J. Hui, R. Smith, S. Cool","doi":"10.1016/j.jcyt.2024.03.116","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.03.116","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141275324","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":"STANDARDIZED METHODS IN IPSC FOR CRISPR-BASED EDITING AND HOMOLOGY-DIRECTED REPAIR (HDR)","authors":"K. Murugan, B.C. Thommandru, S. Glenn, J. Woodley, G. Rettig","doi":"10.1016/j.jcyt.2024.03.470","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.03.470","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141279674","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":"The mesenchymal stromal cell (MSC) secretome promotes tissue regeneration and increases macrophage infiltration in acute and MRSA-infected skin wounds in vivo","authors":"Aarthi Rajesh, Esther Da Eun Ju, Kelly A. Oxford, R. Harman, G. R. Van de Walle","doi":"10.1016/j.jcyt.2024.06.007","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.06.007","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141392265","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":"STABILITY PROGRAM REVALIDATION AND OPTIMIZATION, ONE CENTER EXPERIENCE**","authors":"X. Liu, A. Rivera, A. Pepper, M. Maffie, C. Bertagnolli, T. Shook, L. Gordon, S. Singhal, J. Mehta, F. Zhu","doi":"10.1016/j.jcyt.2024.03.196","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.03.196","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141278613","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":"STERILITY SAMPLING OF CELL, GENE, AND TISSUE THERAPY PRODUCTS (ATMPs)","authors":"T. Wood","doi":"10.1016/j.jcyt.2024.03.233","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.03.233","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141275070","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":"A review and statistical analysis to identify and describe relationships between CQAs and CPPs of natural killer cell expansion processes","authors":"Valentin von Werz, Oliver Spadiut, Bence Kozma","doi":"10.1016/j.jcyt.2024.05.025","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.05.025","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141412014","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}