Biotechnology Progress最新文献_第3页

Near-infrared spectroscopy coupled with convolutional neural network as a checkpoint tool for cell culture bioprocess media characterization. 近红外光谱耦合卷积神经网络作为细胞培养生物过程介质表征的检查点工具。

IF 2.5 3区生物学

Biotechnology Progress Pub Date : 2025-08-11 DOI: 10.1002/btpr.70056

Neelesh Gangwar, Keerthiveena Balraj, Anurag S Rathore

{"title":"Near-infrared spectroscopy coupled with convolutional neural network as a checkpoint tool for cell culture bioprocess media characterization.","authors":"Neelesh Gangwar, Keerthiveena Balraj, Anurag S Rathore","doi":"10.1002/btpr.70056","DOIUrl":"https://doi.org/10.1002/btpr.70056","url":null,"abstract":"As per the quality by design (QbD) paradigm, manufacturers are expected to identify critical raw materials that can contribute to variability in process performance and product quality. Further, manufacturers should be able to characterize and monitor the quality of these critical raw materials. Cell culture medium is universally accepted to be one such critical raw material for monoclonal antibody production. It is complex and comprises hundreds of components in varying proportions that are known to impact a multitude of critical quality attributes of a biotherapeutic product, particularly the post-translational modifications. In this study, a near-infrared (NIR) spectroscopy-based quantification method has been developed for media additives that are known to be potential glycan modulators. A one-dimensional convolution neural network (1D-CNN)-based chemometric model has been developed for estimating galactose and uridine concentrations in the various media formulations. Employing the advantage of data augmentation, the proposed 1D-CNN model delivers excellent prediction statistics (test R2 > 0.9) for predicting both analytes in real time. Further, this model has been used in combination with DoE-based experimental design for prediction of glycosylation using concentrations of media additives as input. In summary, predicted glycosylation distributions were in accordance with actual distribution without significant differences (p > 0.9) in the investigated media formulation. The proposed method and tool can play a critical role in facilitating real-time characterization and control of mammalian cell culture raw materials.","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e70056"},"PeriodicalIF":2.5,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enhancing rapid Protein A performance in monoclonal antibody processing: Anion exchange chromatographic clarification. 提高单克隆抗体处理中Protein A的快速性能：阴离子交换色谱澄清。

IF 2.5 3区生物学

Biotechnology Progress Pub Date : 2025-08-07 DOI: 10.1002/btpr.70061

Andrew Vail, David Chau, Jennifer Heitkamp, Alexei Voloshin

{"title":"Enhancing rapid Protein A performance in monoclonal antibody processing: Anion exchange chromatographic clarification.","authors":"Andrew Vail, David Chau, Jennifer Heitkamp, Alexei Voloshin","doi":"10.1002/btpr.70061","DOIUrl":"https://doi.org/10.1002/btpr.70061","url":null,"abstract":"Clarification fidelity, including reduction of insoluble and soluble contaminants, has been demonstrated to significantly affect the performance and robustness of the Protein A capture chromatography step during the purification of monoclonal antibodies (mAb) and their derivatives expressed in CHO cell cultures. While the vast majority of previous studies have focused on the evaluation of these effects on conventional Protein A resins, in this study, we evaluated such effects on the new membrane- and fiber-based Protein A technologies. Both depth filtration and chromatographic clarification using charged functional fiber approaches have been studied, and we evaluated the effects of these methods on convective Protein A technology cycling robustness, as well as the purity of the product in the elution pool with respect to process-related contaminants. We found that clarification of CHO cell culture using anion exchange (AEX) fiber significantly increases the purity of the mAb in the elution pool with respect to host cell protein (at least 50% less) and DNA (>2 log less) as well as enables a higher number of Protein A cycles (at least 2X increase in fiber-based Protein A cycling lifetime) compared to CHO cell culture fluid clarified with conventional depth filtration. It is likely that this is due to superior DNA and sub-500 nm particle reduction during the chromatographic fiber clarification. This work elucidates the importance of a holistic process strategy when designing a biopharmaceutical purification process.","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e70061"},"PeriodicalIF":2.5,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Methylcellulose has synergistic growth benefits with poloxamer in suspension CHO culture. 甲基纤维素与泊洛沙姆在悬浮CHO培养中具有协同生长效益。

IF 2.5 3区生物学

Biotechnology Progress Pub Date : 2025-08-06 DOI: 10.1002/btpr.70064

Joshua S Katz, Susan Jordan, Hélène Flannery, Christopher Rigdon, Stephen Serrano, Kyle Burgett, Shawn Van Bruggen, James Peacock, Atul Joshi, Shaunak Uplekar, Leslie Wolfe

{"title":"Methylcellulose has synergistic growth benefits with poloxamer in suspension CHO culture.","authors":"Joshua S Katz, Susan Jordan, Hélène Flannery, Christopher Rigdon, Stephen Serrano, Kyle Burgett, Shawn Van Bruggen, James Peacock, Atul Joshi, Shaunak Uplekar, Leslie Wolfe","doi":"10.1002/btpr.70064","DOIUrl":"https://doi.org/10.1002/btpr.70064","url":null,"abstract":"Chemically defined cell culture media used in the growth of mammalian cells for biopharmaceutical applications is a complex mixture of various agents to promote cell growth and function. Poloxamer 188 (P188) is a well-known shear protectant added to media for use in CHO suspension culture but is not without drawbacks. This work explores the use of methylcellulose (MC), a well-known pharmaceutical polymer, in CHO media as an alternative and/or complementary additive to P188. IgG-producing DG44 CHO cell lines were cultured in a variety of suspension systems, up to 3 L reactors, to which MC and/or P188 were added. MC was an effective shear protectant in relatively lower shear systems but is less effective on its own in higher shear cultures. Across the range of conditions studied, MC and P188 were found to have a synergistic benefit with each other, where the combination of both additives produced cultures with higher viable cell densities than cultures containing either additive alone. These results indicate that MC is a viable option for use in media optimization studies as part of ongoing process intensification and optimization for CHO manufacturing.","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e70064"},"PeriodicalIF":2.5,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hands-free from inoculation to harvest: Microbial fermentation with multivariate model to automate induction of recombinant protein expression. 从接种到收获无需动手：微生物发酵与多变量模型自动诱导重组蛋白表达。

IF 2.5 3区生物学

Biotechnology Progress Pub Date : 2025-08-05 DOI: 10.1002/btpr.70055

Jennifer Reid, Andrew Szto, Airong Chen, Patricia Gomes, Craig Kearse, Joyce Ni, Tao Yuan

{"title":"Hands-free from inoculation to harvest: Microbial fermentation with multivariate model to automate induction of recombinant protein expression.","authors":"Jennifer Reid, Andrew Szto, Airong Chen, Patricia Gomes, Craig Kearse, Joyce Ni, Tao Yuan","doi":"10.1002/btpr.70055","DOIUrl":"https://doi.org/10.1002/btpr.70055","url":null,"abstract":"Industrial fermentation continually improves biological process control for a wide range of microorganisms used in multi-billion-dollar industries including industrial enzymes, pharmaceuticals, foods, beverages, commodity chemicals, and bioenergy. In the case of recombinant protein production, batch and fed-batch phases of fermentation are usually followed by an induction phase, where chemical or thermal induction initiates the expression of a target protein. Fed-batch processes are usually automated, whereas \"out-of-the-box\" distributed control systems (DCS) are often unable to define the threshold for induction and respond accordingly. The present study demonstrates the integration of optical density (OD) process analytical technology (PAT) and Lucullus®, a process information management system (PIMS), to enable end-to-end automated fermentation at bench and pilot scale. Data aggregated from tens of fermenter runs and hundreds of offline training measurements enabled the development of an accurate multivariate model to predict OD in real-time. This eliminated the requirement to generate offline correlation models for each OD probe, allowed for model transfer, and incorporated additional predictor terms such as antifoam usage. Automating the induction phase enabled end-to-end fermentation, reducing labor and operational costs while increasing yield through higher reactor utilization within the same time period.","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e70055"},"PeriodicalIF":2.5,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Harvesting AAV by tangential flow filtration using reverse asymmetric membranes. 反不对称膜切向流过滤收集AAV。

IF 2.5 3区生物学

Biotechnology Progress Pub Date : 2025-08-04 DOI: 10.1002/btpr.70059

Xiaolei Hao, Ronny Horax, Xianghong Qian, April Wheeler, Hironobu Shirataki, S Ranil Wickramasinghe

{"title":"Harvesting AAV by tangential flow filtration using reverse asymmetric membranes.","authors":"Xiaolei Hao, Ronny Horax, Xianghong Qian, April Wheeler, Hironobu Shirataki, S Ranil Wickramasinghe","doi":"10.1002/btpr.70059","DOIUrl":"https://doi.org/10.1002/btpr.70059","url":null,"abstract":"Efficient bioreactor clarification for harvesting virus particles is often challenging. Tangential flow filtration is attractive as it can be easily adapted for batch and perfusion operations. Here the feasibility of using reverse asymmetric hollow fiber membranes, where the more open support structure faces the feed stream, has been investigated for harvesting adeno associated virus serotype 2. The open support structure of these membranes stabilizes a secondary membrane consisting of rejected particulate matter. It is essential that the stabilized secondary membrane remains highly permeable. Flux stepping experiments were conducted in total recycle mode in order to determine the critical flux. The critical flux is the maximum stable flux. Higher fluxes lead to a rapid increase in transmembrane pressure under constant flux operation. The critical flux is shown to increase with increasing wall shear rate (feed flow rate). The reduction in turbidity of the permeate relative to the feed decreases with increasing wall shear rate. Harvesting adeno associated virus was conducted at a wall shear rate of 2000 s-1. The permeate flux was set at 15 Lm-2 h-1. The feed was concentrated till the transmembrane pressure reached 3.5 kPa. Diafiltration then commenced using 3 diavolumes. While commencing diafiltration with a smaller feed volume will reduce diluent usage and dilution of the product, it is essential that the transmembrane pressure is not too high to create a compacted low permeability secondary membrane. Here the transmembrane pressure was almost constant at 3.5 kPa during diafiltration. Virus recovery was 94%.","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e70059"},"PeriodicalIF":2.5,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Innovations in Dental Implants Integration: Optimizing dental implants performance utilizing stem cells and coatings. 牙种植体整合创新：利用干细胞和涂层优化牙种植体性能。

IF 2.5 3区生物学

Biotechnology Progress Pub Date : 2025-08-01 DOI: 10.1002/btpr.70060

Ioannis Tsamesidis, Athanasios Christodoulou, Evangelia Stalika, Georgia K Pouroutzidou, Eleana Kontonasaki

{"title":"Innovations in Dental Implants Integration: Optimizing dental implants performance utilizing stem cells and coatings.","authors":"Ioannis Tsamesidis, Athanasios Christodoulou, Evangelia Stalika, Georgia K Pouroutzidou, Eleana Kontonasaki","doi":"10.1002/btpr.70060","DOIUrl":"https://doi.org/10.1002/btpr.70060","url":null,"abstract":"The last two decades, between 2000 and 2024, significant steps were achieved regarding the interaction between various stem cells and titanium implant surfaces to improve dental implant integration. This literature review focuses on the potential effects of (i) bone marrow mesenchymal stem cells (BMSCs), (ii) periodontal ligament stem cells (PDLSCs), and (iii) dental follicle stem cells (DFSCs) in promoting osseointegration and tissue regeneration. Studies have shown that combining these stem cells with Ti implants enhances bone formation, accelerates implant osseointegration, and improves long-term implant stability. Additionally, animal models and bioreactors have been employed to evaluate the effects of stem cells on dental implant performance, with some studies showing promising results, although certain models have also yielded inconsistent outcomes. The interaction between stem cells and surface-modified Ti implants has emerged as a key area of research, with results indicating improved healing times and reduced failure rates. This article provides an overview of these findings, highlighting the role of stem cells in not only replacing lost teeth but also actively regenerating the surrounding biological structures for a more integrated and natural outcome.","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e70060"},"PeriodicalIF":2.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Accelerating AAV purification process development using high-throughput resin tip module. 利用高通量树脂尖端模块加速AAV净化工艺的开发。

IF 2.5 3区生物学

Biotechnology Progress Pub Date : 2025-07-18 DOI: 10.1002/btpr.70053

Qingxuan Li, Mahsa Hadidi, Steven Benner, Junfen Ma

{"title":"Accelerating AAV purification process development using high-throughput resin tip module.","authors":"Qingxuan Li, Mahsa Hadidi, Steven Benner, Junfen Ma","doi":"10.1002/btpr.70053","DOIUrl":"https://doi.org/10.1002/btpr.70053","url":null,"abstract":"Recombinant adeno-associated viruses (AAVs) with precise genome editing and cell-virus interaction have become a promising delivery tool for gene therapy. A robust AAV purification process is crucial for ensuring therapeutic efficacy. The challenges of AAV purification process development encompass limited material availability during early-stage development, high cost-of-goods compared to traditional biologics, and short development timelines for the critical first-in-human stages. The key to overcoming these challenges is to leverage high throughput (HTP) methods. In this article, an integrated end-to-end HTP workflow is proposed, utilizing a resin tip as the purification module and incorporating an HTP analytical toolkit on one platform. Purification parameters, including binding capacity, resin selection, and buffer composition screening for AAV full/partial/empty capsids separation, are efficiently determined using a 25 μL resin tip and HTP analytical tools with only micro-volume sample requirements. The process parameters determined from the HTP workflow predict the trends of full capsid enrichment and partial capsid removal for the bench-scale purification. This HTP workflow is also applied for the assessment of the AAV quality attributes to accelerate early-stage cell line and cell culture development. Comparable AAV quality attributes are demonstrated to Robocolumn as the benchmark HTP purification method. By leveraging HTP analytical tools to instantly interpret the purification data, this integrated HTP workflow effectively accelerates AAV purification process development, with a 2% material volume requirement compared to the benchmark method, 96-well format screening, short turnaround time for analytical assays, and significant cost-of-goods savings for downstream process development.","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e70053"},"PeriodicalIF":2.5,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PEGylation of polymerized albumin retains colloid osmotic pressure: Towards an enhanced potential plasma substitute. 聚合白蛋白的聚乙二醇化保持胶体渗透压：迈向增强的潜在血浆替代品。

IF 2.5 3区生物学

Biotechnology Progress Pub Date : 2025-07-14 DOI: 10.1002/btpr.70054

Amna Abdalbaqi, Ahmad Yahya, Krianthan Govender, Carlos Muñoz, Gala Sanchez Van Moer, Daniela Lucas, Pedro Cabrales, Andre F Palmer

{"title":"PEGylation of polymerized albumin retains colloid osmotic pressure: Towards an enhanced potential plasma substitute.","authors":"Amna Abdalbaqi, Ahmad Yahya, Krianthan Govender, Carlos Muñoz, Gala Sanchez Van Moer, Daniela Lucas, Pedro Cabrales, Andre F Palmer","doi":"10.1002/btpr.70054","DOIUrl":"https://doi.org/10.1002/btpr.70054","url":null,"abstract":"Plasma expanders (PEs) are commonly used to replace lost blood volume for septic shock patients with increased vascular permeability. Human serum albumin (HSA) is the preferred PE, due to its innate ability to restore blood colloid osmotic pressure (COP). However, HSA is susceptible to protein extravasation under endothelial dysfunction leading to edema and exposing tissue to toxic HSA-bound metabolites. To prevent extravasation, the molecular diameter of HSA has been previously increased through chemical polymerization to yield polymerized HSA (PHSA). In this study, we further optimize PHSA size and COP via polyethylene glycol (PEG) surface conjugation. Previously synthesized PHSA that was size fractionated via tangential flow filtration (TFF) into two brackets (bracket A [500 kDa-0.2 μm] and bracket B [50-500 kDa]) served as precursors for subsequent PEGylation. Each PHSA bracket was thiolated with 2-iminothiolane hydrochloride (IT) and PEGylated with monofunctional 5 kDa maleimide PEG to yield PEGylated PHSA (PPHSA). All PPHSA solutions exhibited increased molecular size, zeta potential, and osmolality compared to their non-PEGylated precursor PHSA. At the same total protein concentration, PPHSA viscosity decreased compared to the precursor PHSA, while the COP remained consistent with HSA, indicating their potential to serve as PEs.","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e70054"},"PeriodicalIF":2.5,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RETRACTION: A Novel pH-Responsive Nanoniosomal Emulsion for Sustained Release of Curcumin from a Chitosan-Based Nanocarrier: Emphasis on the Concurrent Improvement of Loading, Sustained Release, and Apoptosis Induction 摘要：一种新型的ph响应纳米乳剂，用于从壳聚糖为基础的纳米载体中缓释姜黄素：重点是同时改善负载，缓释和诱导细胞凋亡。

IF 2.5 3区生物学

Biotechnology Progress Pub Date : 2025-06-25 DOI: 10.1002/btpr.70038

{"title":"RETRACTION: A Novel pH-Responsive Nanoniosomal Emulsion for Sustained Release of Curcumin from a Chitosan-Based Nanocarrier: Emphasis on the Concurrent Improvement of Loading, Sustained Release, and Apoptosis Induction","authors":"","doi":"10.1002/btpr.70038","DOIUrl":"10.1002/btpr.70038","url":null,"abstract":"RETRACTION: S. Haseli, M. Pourmadadi, A. Samadi, F. Yazdian, M. Abdouss, H. Rashedi, and M. Navaei-Nigjeh, “ A Novel pH-Responsive Nanoniosomal Emulsion for Sustained Release of Curcumin from a Chitosan-Based Nanocarrier: Emphasis on the Concurrent Improvement of Loading, Sustained Release, and Apoptosis Induction,” Biotechnology Progress 38, no. 5 (2022): e3280, https://doi.org/10.1002/btpr.3280.The above article, published online on 30 June 2022 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, John A. Morgan; the American Institute of Chemical Engineers; the Society for Biological Engineering; and Wiley Periodicals LLC.The retraction has been agreed upon following an investigation into concerns raised by a third party, which revealed inappropriate duplication of image panels between this (Figure 4) and another article published by an overlapping group of authors, depicting a different experimental condition.The partial raw data provided by the authors could not address the original concerns, showed inconsistencies with the published results, and ultimately raised additional doubts about the study's overall reliability. Consequently, the editors have lost confidence in the presented data and decided to retract the paper. The authors’ institute has been informed of the allegations and the decision to retract but remained unresponsive. The authors disagree with the retraction.","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":"41 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://aiche.onlinelibrary.wiley.com/doi/epdf/10.1002/btpr.70038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A digital shadow of CAR T cell expansion in a perfusion bioreactor: Informing optimal harvest times for autologous cell therapy. 灌注生物反应器中CAR - T细胞扩增的数字阴影：告知自体细胞治疗的最佳收获时间。

IF 2.5 3区生物学

Biotechnology Progress Pub Date : 2025-06-23 DOI: 10.1002/btpr.70045

Joseph R Egan, Núria Marí-Buyé, Elia Vallejo Benítez-Cano, Miquel Costa, Linda Wanika, Michael J Chappell, Ursula Schultz, Jelena Ochs, Manuel Effenberger, David Horna, Qasim Rafiq, Stephen Goldrick

{"title":"A digital shadow of CAR T cell expansion in a perfusion bioreactor: Informing optimal harvest times for autologous cell therapy.","authors":"Joseph R Egan, Núria Marí-Buyé, Elia Vallejo Benítez-Cano, Miquel Costa, Linda Wanika, Michael J Chappell, Ursula Schultz, Jelena Ochs, Manuel Effenberger, David Horna, Qasim Rafiq, Stephen Goldrick","doi":"10.1002/btpr.70045","DOIUrl":"https://doi.org/10.1002/btpr.70045","url":null,"abstract":"Chimeric antigen receptor (CAR) T cell therapy has tremendous potential for the treatment of cancer and other diseases. To manufacture cells of the desired quantity and quality, it is important to expand the CAR T cells ex vivo for an optimal duration. However, identifying the optimal harvest time requires knowledge of the cell concentration during the expansion period. To address this challenge, we have developed a digital shadow of CAR T cell expansion that provides a soft sensor of cell concentration in real-time. Specifically, a novel mechanistic mathematical model of cell growth within a proportional-integral-derivative (PID) controlled perfusion bioreactor has been developed using nonlinear ordinary differential equations. The model is fitted to data generated via bioreactor runs of the Aglaris FACER, in which both donor and patient cells have been expanded in two different media. Off-line data includes the initial and final cell concentrations, and online data includes the glucose and lactate concentrations as well as the perfusion rate. Training the digital shadow utilizes all the off-line and online data for each run. In contrast, real-time testing utilizes only the initial cell concentration and the available online data at the time of model fitting. Real-time testing shows that with at least 2.5 days of online data, the final cell concentration up to 2.5 days later is predicted with a mean relative error of 13% (standard deviation ≈ 6%). Informative real-time predictions of cell concentration via the digital shadow can guide decisions regarding the optimal harvest time of CAR T cells.","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e70045"},"PeriodicalIF":2.5,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0