Cytotherapy最新文献

{"title":"Efficacy and risk of donor-derived CAR-T treatment of relapsed B-cell acute lymphoblastic leukemia after hematopoietic stem cell transplantation","authors":"","doi":"10.1016/j.jcyt.2024.05.021","DOIUrl":"10.1016/j.jcyt.2024.05.021","url":null,"abstract":"<div><div>The one-year survival rate for patients experiencing a relapse of B-cell acute lymphocytic leukemia (B-ALL) following hematopoietic stem cell transplantation (HSCT) is approximately 30%. Patients experiencing a relapse after allogeneic HSCT frequently encounter difficulties in obtaining autologous CAR-T products. We conducted a study involving 14 patients who received donor-derived CAR-T therapy for relapsed B-ALL following HSCT between August 2019 and May 2023 in our center. The results revealed a CR/CRi rate of 78.6% (11/14), a GVHD rate of 21.4% (3/14), and a 1-year overall survival (OS) rate of 56%. Decreased bone marrow donor cell chimerism in 9 patients recovered after CAR-T therapy. The main causes of death were disease progression and infection. Further analysis showed that GVHD (HR 7.224, 95% CI 1.42–36.82, <em>P</em> = 0.017) and platelet recovery at 30 days (HR 6.807, 95% CI 1.61–28.83, <em>P</em> = 0.009) are significantly associated with OS after CAR-T therapy. Based on the findings, we conclude that donor-derived CAR-T cells are effective in treating relapsed B-ALL patients following HSCT. Additionally, GVHD and poor platelet recovery impact OS, but further verification with a larger sample size is needed.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421769","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":"Minimal information for studies of extracellular vesicles 2023: relevance to cell and gene therapies","authors":"Kenneth W. Witwer","doi":"10.1016/j.jcyt.2024.05.018","DOIUrl":"10.1016/j.jcyt.2024.05.018","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1465324924007278/pdfft?md5=41623862923d3653142d2f9a2e9a374a&pid=1-s2.0-S1465324924007278-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141753325","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":"CHIMERIC ANTIGEN RECEPTOR (CAR) T CELL THERAPY FOR ASPERGILLOSIS.","authors":"P. Kumar ,&nbsp;S. Wurster ,&nbsp;T. daSilva ,&nbsp;P. Hauser ,&nbsp;S.S. Neelapu ,&nbsp;D. Kontoyiannis","doi":"10.1016/j.jcyt.2024.03.020","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.03.020","url":null,"abstract":"<div><h3>Background &amp; Aim</h3><p>Invasive aspergillosis (IA) is a common and deadly mold infection in immunocompromised patients. As morbidity and mortality of IA are primarily driven by poor immune defense, adjunct immunotherapies, such as CAR T cells, are direly needed. Here, we propose a novel approach to generate <em>Aspergillus fumigatus</em> (AF)-CAR T cells using the scFv domain of AF-269-5 mAb and a lentiviral vector system.</p></div><div><h3>Methods, Results &amp; Conclusion</h3><p>Targeting domain of the AF-CAR construct was designed from the CDR sequence of AF-269-5 monoclonal antibody. The targeting domain was fused to the hinge and transmembrane domains of human CD8α and the cytoplasmic signaling domains of CD137/4-1BB and CD3ζ and subcloned in LV vector dCAS9-VP64-GFP (Addgene, Water Town, USA).</p><p>These cells successfully targeted mature hyphal filaments of representative clinical and reference AF isolates and elicited potent release of cytotoxic effectors and type 1 T-cell cytokines. Furthermore, AF-CAR T cells generated from peripheral blood mononuclear cells of four healthy human donors and expanded with cytokine stimulation (IL-2, IL-7+IL-15) regimens significantly suppressed mycelial growth of AF-293 after 18 h of co-culture and synergized with the immunomodulatory antifungal agent caspofungin to control hyphal growth for 36 hours. Moreover, cyclophosphamide-immunosuppressed NSG mice with invasive pulmonary aspergillosis that received two doses of 5 million AF-CAR T cells on days 0 and 2 after AF infection showed significantly reduced morbidity on day 4 post-infection (p&lt;0.001) and significantly improved 7-day survival (p=0.049) compared to mice receiving non-targeting control T cells. This newly developed construct has several major advantages in its design and mode of action compared to published AF-reactive CAR T-cell products: (i) Unlike Dectin-1 CAR T cells that have weak affinity to mature mycelium, our present product was designed to efficiently target mature AF hyphae. (ii) Our AF-CAR T cells could enable generation of clinical-grade AF-CAR T cells for large scale production in a time frame of 3-7 days.</p><p>In conclusion, we developed a novel lentiviral strategy to obtain AF-CAR T cells with high targeting efficacy, yielding significant anti-AF activity <em>in vitro</em> and short-term protection <em>in vivo</em>. These results underscore the promise of anti-<em>Aspergillus</em> immunotherapy and provide a novel approach for efficient production of AF-CAR T cells for future clinical translation after further in-depth evaluation.</p></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141077579","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":"Welcome to ISCT 2024","authors":"","doi":"10.1016/S1465-3249(24)00614-5","DOIUrl":"https://doi.org/10.1016/S1465-3249(24)00614-5","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141077654","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":"SIZE-BASED MICROFLUIDIC-ENRICHED MESENCHYMAL STEM CELL SUBPOPULATION ENHANCED ARTICULAR CARTILAGE REPAIR","authors":"Z. Yang ,&nbsp;Y. Wu ,&nbsp;S. Neo ,&nbsp;D. Yang ,&nbsp;L.A. Boyer ,&nbsp;E. Lee ,&nbsp;J. Han","doi":"10.1016/j.jcyt.2024.03.030","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.03.030","url":null,"abstract":"<div><h3>Background &amp; Aim</h3><p>The functional heterogeneity development of culture-expanded mesenchymal stem cells (MSCs) has hindered the clinical consistency of MSC. Previous studies have shown that MSC subpopulations with superior chondrogenic capacity can be isolated using a spiral microfluidics device based on the principle of inertial cell focusing. This study aims to demonstrate that the implantation of microfluidic-enriched chondrogenic MSCs that are consistent in size and function would overcome the challenge of functional heterogeneity of expanded MSC, and will significantly improve MSC-based cartilage repair.</p></div><div><h3>Methods, Results &amp; Conclusion: Methods</h3><p>A next-generation, fully automated multi-dimensional double spiral (MDDS) microfluidic device was designed to provide more refined size resolution and efficient isolation of the MSC subpopulation based on size. In vitro chondrogenic potential and RNA sequencing analysis was performed on the size-sorted MSC subpopulations. The <em>in vivo</em> cartilage repair efficacy was demonstrated in a 12 weeks old rat osteochondral injury model. Defects were implanted with MSC subpopulations (n=6 per group) and was compared with implantation of the un-segregated MSCs (n=6). Osteochondral repair was assessed at 6 and 12 weeks post-surgery by histological, micro-computed tomography (micro-CT) and mechanical analyses.</p></div><div><h3>Results</h3><p>A chondrogenic subpopulation of MSC was efficiently isolated using the MDDS device. RNA sequencing analysis revealed distinct transcriptomic profiles and identified differential gene expression between subpopulations. Delivery of chondrogenic MSC subpopulation resulted in improved cartilage repair as indicated by histological scoring, compressional modulus, and micro-CT analysis of the subchondral bone.</p></div><div><h3>Conclusion</h3><p>We have established a rapid, label-free, and reliable microfluidic protocol for more efficient size-based enrichment of a chondrogenic subpopulation of MSC. The delivery of microfluidics-enriched chondrogenic MSCs that are consistent in size and function can overcome the challenge of functional heterogeneity of expanded MSCs, resulting in significant improvement in MSC-based cartilage repair. The availability of such rapid, label-free enriched chondrogenic MSCs can enable better cell therapy products for cartilage repair with improved treatment outcomes.</p></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141077954","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":"FULLY-AUTOMATED CULTIVATION OF IPSCS AND DIFFERENTIATION TO IMSCS USING THE AUTOCRAT SYSTEM","authors":"L. Herbst ,&nbsp;A. Felser ,&nbsp;F. Groten ,&nbsp;G. Shaw ,&nbsp;M. Murphy ,&nbsp;B. Nießing ,&nbsp;R. Schmitt","doi":"10.1016/j.jcyt.2024.03.082","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.03.082","url":null,"abstract":"<div><h3>Background &amp; Aim</h3><p>Although major developments in the field of regenerative medicine have been made, osteoarthritis (OA) remains one of the major illnesses of our day. Mesenchymal stem cells (MSCs) have been suggested as a potential therapy for OA. The clinical success of MSCs has been mixed with several successful phase I and II trials and some phase III trials questioning the efficacy of MSCs as a treatment for OA. These mixed results are partly is attributed to the high degree of biologic variability and lack of standardisation across the manufacturing process of MSCs. MSCs derived from induced pluripotent stem cells (iPSCs) might address some of the heterogeneity derived from donor-to-donor variability. On the manufacturing side, automation is a key technology to increase standardisation and improve iMSC manufacturing in cell quality and manufacturing efficiency.</p></div><div><h3>Methods, Results &amp; Conclusion</h3><p>In the EU project AutoCRAT the systems Autostem and StemCellDiscovery are combined to a fully-automated system for the manufacturing of iPSCs, differentiation to iMSCs and chondrocytes, as well as MSC derived extracellular vesicles (EVs). The Autostem system was previously developed for automated bioreactor-based MSC expansion and subsequent fill-and-finish. For AutoCRAT it was adapted to allow manufacturing of iMSCs and iMSC derived extracellular vesicles (EVs). Similarly, the StemCellDiscovery was developed for plate-based MSC cultivation and microscopic evaluation. This system was adapted to allow for iPSC cultivation and differentiation of iPSCs to iMSCs and chondrocytes.</p><p>This talk reports on the evaluation of this automated solution using a direct comparison of automated versus manual cultivation of iMSCs and iPSCs in terms of efficiency and cell quality. More importantly, it compares manual and automated differentiation of iPSCs to iMSCs. This comparison clearly illustrates the automated system is highly capable in the cultivation of iPSCs and iMSCs. The morphology and fold expansion of iPSCs and iMSCs manufactured in an automated setting is comparable to the manual cultivation. The immunofluorescence and flow cytometry results confirm the automated system is capable of manufacturing high-quality iPSCs and iMSCs. Comparing automated and manual differentiation of iPSCs to iMSCs illustrates the capabilities of the AutoCRAT system in manufacturing of iPSC derived cell therapies. The data presented here highlights the importance of automation for the standardised and transparent manufacturing of cell therapies.</p></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141078302","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(24)00604-2","DOIUrl":"https://doi.org/10.1016/S1465-3249(24)00604-2","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141078316","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":"EXOSOMES AS A STROMAL-TARGETING EXTENSION OF ONCOLYTIC VIRUS THERAPEUTICS","authors":"K.R. Friesen ,&nbsp;D. Gupta ,&nbsp;K.D. Fisher ,&nbsp;M. Wood ,&nbsp;L.W. Seymour","doi":"10.1016/j.jcyt.2024.03.054","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.03.054","url":null,"abstract":"<div><h3>Background &amp; Aim: Background</h3><p>Oncolytic viruses (OVs) selectively replicate in and kill cancer cells. OVs can be used as a gene delivery vector for selective expression of therapeutics in the tumour microenvironment (TME). One current barrier of OV-mediated therapy in solid tumours is the poor viral spread due to the extracellular matrix produced from stromal cells such as cancer-associated fibroblasts (CAFs).</p><p>Exosomes are lipid-coated nanoparticles which can be engineered to transport therapeutics between donor and recipient cells.</p></div><div><h3>Aim</h3><p>To enhance the spread of therapeutics <em>in situ</em>, we are developing an exosome-targeting system where DNA coding for a tripartite fusion protein (consisting of a targeting protein (anti-FAP scFv), a scaffold protein, and a therapeutic protein (cytosine deaminase)) is delivered by an oncolytic adenovirus. The fusion protein is synthesized and loaded into exosomes for delivery to surrounding potentially non-infected tumour and stromal cells such as CAFs.</p></div><div><h3>Methods, Results &amp; Conclusion: Methods</h3><p>Exosomes were isolated via size exclusion chromatography from adenocarcinoma cells stably transduced with the tripartite fusion protein and characterized according to MISEV guidelines. Real-time exosome uptake into cancer cells and CAFs was monitored using a split nanoluciferase reporter system. Nano-flow cytometry and a FlipGFP-reporter system were used to evaluate the functionality and targeting potential of the anti-FAP scFv exosmes. Cell viability assays were used to quantify the ability of exosomes to deliver cytosine deaminase to cancer cells and CAFs.</p></div><div><h3>Results</h3><p>Exosomes containing a subunit of split nanoluciferase were capable of being taken up in real-time and delivering functional cargo into the cytoplasm of recipient tumour cells expressing the other subunit. A functional anti-FAP scFv was capable of being expressed on exosomes, and exosomes armed with cytosine deaminase resulted in a significant decrease in tumour cell viability following the addition of 5-fluorocytosine.</p></div><div><h3>Conclusion</h3><p>Exosomes can be engineered to selectively package therapeutics and deliver cargo to recipient cells resulting in target cell death. The cytotoxicity of the oncolytic virus expressing the tripartite fusion protein is currently being evaluated using these methods <em>in vitro</em> and <em>ex vivo</em>. Concentrating the production of bioengineered EVs directly in the TME provides a novel approach to overcome the biodistribution and rapid EV clearance challenges that limit the clinical potential of therapeutic Exosomes/EVs.</p></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141078354","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":"ALLOGENEIC UMBILICAL-CORD DERIVED MESENCHYMAL STROMAL CELLS MSC(UC) AS TREATMENT FOR SYSTEMIC LUPUS ERYTHEMATOSUS (SLE): SAFETY AND EARLY CLINICAL/BIOLOGICAL RESULTS FROM A PHASE I-II PROOF-OF-CONCEPT CLINICAL STUDY","authors":"D. Farge ,&nbsp;L. Biard ,&nbsp;B. Weil ,&nbsp;S. Loisel ,&nbsp;P. LANSIAUX ,&nbsp;I. Munia ,&nbsp;V. Girault ,&nbsp;C. Charles ,&nbsp;A. Korganow ,&nbsp;C. Beuvon ,&nbsp;G. Pugnet ,&nbsp;C. Cacciatore ,&nbsp;N. Abisror ,&nbsp;J. Taupin ,&nbsp;A. Cras ,&nbsp;M. Lowdell ,&nbsp;K. Tarte","doi":"10.1016/j.jcyt.2024.03.076","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.03.076","url":null,"abstract":"<div><h3>Background &amp; Aim: Background</h3><p>Preclinical studies show Mesenchymal Stromal Cells (MSC) unique immunomodulatory, proangiogenic, and antifibrotic effects. Few clinical data report MSC use to treat Systemic Lupus (SLE) patients (pts) resistant to standard immunosuppressors and biologics, who suffer from high morbidity and increased mortality.</p></div><div><h3>Aims</h3><p>To test the safety and preliminary efficacy of a single intravenous injection of allogeneic umbilical cord-derived (UC) MSC in severe SLE<strong>.</strong></p></div><div><h3>Methods, Results &amp; Conclusion: Methods</h3><p>A prospective, single-center, Bayesian phase I/II study (NCT03562065) enrolled SLE pts (ACR criteria + antinuclear antibodies), aged 18–70 years (yr) with active disease (SELENA-SLEDAI-2K ≥6) at baseline and refractory to <u>&gt;</u>2 immunosuppressive therapies for at least 3 months (M), including Prednisone ≥ 6 mg daily for ≥ 28 days, to receive a single infusion of 2 or 4.10⁶ MSC(UC)/kg obtained from a single UC. Primary endpoint was the rate of treatment-related (TR) severe adverse events (SAE, grade ≥ 3) in the first 10 days post-MSC(UC) infusion. Secondary endpoints were adequacy of MSC(UC) production, all AE, clinical, HrQol and immune responses at M1 and quarterly for 1 yr post-infusion.</p></div><div><h3>Results</h3><p>From Sept 2019 to Feb 2023, 8 (7 female) pts, median age 35 [IQR 27-60] yrs after 12 [6-21] yrs SLE duration, were included with PGA 2 [1.5-2], SELENA-SLEDAI-2K 11.5 [8-14.2], BILAG A (50%), B (38%) or C (12%) and SLICC-ACR 1.5 [0-2.8] prior MSC(UC) infusion (median dose 2 [IQR 2-4]x10⁶/kg). All pts received ≥2.10⁶/kg MSC(UC) (5 assigned to 2.10⁶/kg, 3 to 4.10⁶/kg) with 1 batch released at lower than expected target dose. No SAE and 3 infusion-related AE (2 grade 1, 1 grade 2) in 2 pts occurred in the first 10 days. After 12.4 (min 9.6-max 13) months of follow-up, there were no TR SAE and 3 non-TR SAE after relapse in 1 pt. Improved clinical status (Table) in 7/8 pts at M3 persisted over 1 yr with 2 major and 2 partial clinical responses at M12. Donor-specific anti-HLA antibodies developed <em>de novo</em> in 1 pt at M3. While circulating T, B, NK and monocytes were unmodified by MSC(UC), CD24^hiCD38^hi transitional and CD27^posCD38^neg/loCD24^hi memory B-cells frequencies, i.e. regulatory B-cell subsets, increased significantly and transiently at M1.</p></div><div><h3>Conclusion</h3><p>A single infusion of MSC(UC) was safe in 8 severe SLE pts. This proof of concept study showed clinical improvement. Placebo-controlled trials are needed to confirm clinical efficacy and explore the role of B-cell modifications in clinical benefit.</p></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141077731","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 OF AN AUTOMATED CRYOPRESERVATION PROCESS FOR LEUKAPHERESIS TO SUPPORT CGT SUPPLY CHAIN.","authors":"G. Delwiche ,&nbsp;A. Fossion ,&nbsp;S. Borensztein ,&nbsp;G. Fonkou Tchinda ,&nbsp;D. Delvaux ,&nbsp;J. Bravo-Alegria ,&nbsp;A. Michaux","doi":"10.1016/j.jcyt.2024.03.041","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.03.041","url":null,"abstract":"<div><h3>Background &amp; Aim</h3><p>Cryoport Systems is the global market leader in temperature-controlled supply chain solutions for critical materials in the life sciences industry and is currently supporting the Cell Therapy Industry with IntegriCell™ – an integrated Leukapheresis Supply Chain Platform. IntegriCell™ aims to deliver consistent, compliant, high-quality leukapheresis starting material for use in the manufacture of cell-based therapies leading to cost reduction through optimized manufacturing slot scheduling.</p><p>Cell therapies require an optimized cryopreservation process to achieve consistent results. Cryoport Systems, through the IntegriCell™ platform, is building a network of cryopreservation centers across the US and EU to ensure close proximity to patients, and to optimize and standardize cryopreservation of leukapheresis together within an integrated storage and distribution network.</p></div><div><h3>Methods, Results &amp; Conclusion</h3><p>Here, we illustrate the development of an automated closed process using the Cue® Cell Processing System from Fresenius Kabi. This process is subdivided into buffer preparation; Cue system processing, post processing and freezing. Cue system processing is a critical step which involves wash of leukapheresis by spinning membrane filtration, buffer exchange and cryo-formulation. We developed a Quality by Design process upon which Quality Target Product Profile (QTPP) for cryopreserved leukapheresis was defined. In addition, Critical Quality Attributes (CQAs), Critical Material Attribute (CMAs) and Critical Process parameters (CPPs) were identified based on Risk Assessment. Built on those prerequisites, an Automated closed cryo-process was developed by optimizing CPPs such as wash buffer solution content, cell concentration upon processing and spinner wash flow rate.</p><p>Data obtained upon development justified the CQAs for cryopreserved leukapheresis with ≥80% process recovery and ≥90% viability after thawing. The results also demonstrated that buffer exchange did not significantly modifies the profile of the original fresh leukopack. Together, the automated closed process leads to reduced variability in post thaw recovery and viability compared to the more traditional manual processes. This confirming the capacity of the IntegriCell™ automated process to reduce product variability for the CGT manufacturers. This study highlights the benefits of using the IntegriCell Automated Cryopreservation Process for improving process and product consistency of the starting leukapheresis for CGT manufacturing.</p></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141077955","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}