Cytotherapy最新文献

{"title":"Quantitative Predictive Cellular Analytics Driving Improvements in Advanced Therapy Development and Manufacturing","authors":"C. Hebert ,&nbsp;M. Elahy ,&nbsp;Z. Evans ,&nbsp;A. Kersey ,&nbsp;M. Lowry ,&nbsp;S.J. Hart","doi":"10.1016/j.jcyt.2025.03.020","DOIUrl":"10.1016/j.jcyt.2025.03.020","url":null,"abstract":"<div><h3>Background &amp; Aim</h3><div>Advanced therapy medicinal products (ATMPs) such as chimeric antigen receptor (CAR) T-cell therapies have shown great success, but challenges remain. These include variability in patient and donor cell quality and complex manufacturing processes, highlighting the need for robust analytical methods to ensure quality and consistency while increasing access. Process automation offers benefits, but fit-for-purpose cell-based analytics are crucial for providing predictive and prescriptive insights from R&amp;D through manufacturing and quality control (QC). Connecting analytics throughout the development and manufacturing process can reduce the need for comparability studies, lower costs, and improve product quality. This study provides data supporting Laser Force Cytology (LFC) as a comprehensive cell-based analytical tool for use throughout the entire CAR T-cell development process, including donor screening, process development, monitoring, and QC.</div></div><div><h3>Methodology</h3><div>LumaCyte's Radiance® instrument uses LFC, combining optical and hydrodynamic force measurements to analyze single cells without the need for antibodies or fluorescent labels. To demonstrate the technology, naive, mock transduced, and CD19+ CAR T cells were manufactured from healthy human donors. Transduced cells were incubated with NALM6 cells for a 24h period at different effector:target cell ratios. After the 24h incubation period, co-cultures and monocultures were analyzed using LFC and in parallel monitored for luciferase activity, which served as an orthogonal measurement of the NALM6 cell killing.</div></div><div><h3>Results</h3><div>Co-culture assay results demonstrated a strong correlation between the killing efficacy measured using the label-free LFC data with the orthogonal luciferase assay. After establishing the co-culture killing capacity of each manufactured CAR T cell lot, donors were classified as either high or low-killing efficiency. Using the LFC analysis of the PBMC starting materials from each donor, the classification as either high or low-killing efficiency could be predicted.</div></div><div><h3>Conclusion</h3><div>LFC precisely measures subtle cellular changes, providing near real-time data that enables donor and process prediction to speed process development and ultimately improve manufacturing and clinical outcomes. Our data demonstrate how this novel technology improves CGT development and production assays, compress development time, and reduces costs for these life-saving treatments.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 5","pages":"Page S17"},"PeriodicalIF":3.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888147","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":"Perfusion-powered production of over 100 CAR-T doses in a 2-litre stirred-tank bioreactor with automated product harvest, wash and concentration","authors":"P. Springuel ,&nbsp;F. Slingsby ,&nbsp;N. Bevan ,&nbsp;A. Frangleton ,&nbsp;M. Szelwicki ,&nbsp;T. Schmidberger ,&nbsp;A. Ahmad ,&nbsp;E. Pineda ,&nbsp;R. Legmann ,&nbsp;R. Gantier ,&nbsp;R. Ladi ,&nbsp;N. Dianat ,&nbsp;J. Hengst ,&nbsp;Q. Rafiq","doi":"10.1016/j.jcyt.2025.03.023","DOIUrl":"10.1016/j.jcyt.2025.03.023","url":null,"abstract":"<div><h3>Background &amp; Aim</h3><div>Allogeneic CAR-T therapies offer the potential to mass produce \"off-the-shelf\" doses, addressing the limitations of lengthy manufacturing processes in approved autologous products. To realise this potential, industrially scalable upstream and downstream workflows are required. To this end, we characterised a CAR-T cell perfusion manufacturing process in a 2-litre stirred-tank bioreactor (STR), with a solution to automate the bioreactor harvest, final product wash, and concentration steps.</div></div><div><h3>Methodology</h3><div>Healthy donor-derived anti-CD19 CAR-T cells were cultured in parallel in the Ambr® 250 High Throughput Perfusion and Univessel® 2-litre single-use STR, the latter coupled with the XCell ATF® 2 cell retention device. CAR-T cells were expanded in 4Cell® Nutri-T serum-free medium in perfusion for seven days, and performance was benchmarked against a G-Rex® 24 well plate process. The Ksep® 400 was evaluated as a closed, automated solution for the harvesting, concentration, and washing of the final CAR-T product from the 2L STR. Comparability between the 250mL and 2L systems was examined, alongside the impact of automated harvesting on cell yield, viability, activation, maturation, exhaustion, cytotoxicity, and cytokine release.</div></div><div><h3>Results</h3><div>CAR-T cells were successfully expanded ∼125-fold in perfusion in both 250mL and 2L STRs. At the 2L scale, final yields of ∼50 billion total viable cells were consistently generated, with a CAR transduction efficiency of 34%, corresponding to over 100 representative doses of 150 × 10⁶ CAR+ T cells. Harvested cells were predominantly in the naive and central memory subset (&gt;95%) and expressed negligible levels of exhaustion markers (&lt;1%). No statistical differences were observed in CAR-T cell yield, viability, surface marker expression, or cytotoxicity between the 250mL and 2L bioreactors. Automated harvesting recovered &gt;90% of the total yields, concentrated cells 8-fold, and had no impact on CAR-T cell phenotype, cytotoxicity, or growth kinetics post-harvest.</div></div><div><h3>Conclusion</h3><div>These findings demonstrate the feasibility of multi-litre expansion of functional CAR-T cells to generate hundreds of doses in perfusion-based stirred-tank bioreactors. The Ambr® 250 effectively served as a scaled-down model and facilitated seamless scale-up to 2L. Finally, automated harvesting and concentration streamlined the downstream workflow while maintaining CAR-T cell quality. This scalable upstream and downstream workflow is ideally suited for mass production of future allogeneic therapies.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 5","pages":"Pages S18-S19"},"PeriodicalIF":3.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888150","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":"Human amnion epithelial cells and secretome drive the generation of tolerogenic macrophages and decidua-like NK cells with lower proliferative capability and higher effector functions","authors":"M. Della Lastra ,&nbsp;I. Airoldi ,&nbsp;L. Zeijlon ,&nbsp;F. Morandi ,&nbsp;J. Raffetseder ,&nbsp;R. Gramignoli","doi":"10.1016/j.jcyt.2025.03.066","DOIUrl":"10.1016/j.jcyt.2025.03.066","url":null,"abstract":"<div><h3>Background &amp; Aim</h3><div>Pregnancy is characterized by major immunomodulatory strategies. We previously reported different immune regulatory properties offered by amnion epithelial cells (AEC), isolated from term human placentae. Once transplanted in immune-competent recipients, AEC engrafted and survived, boosting the innate capacity for regeneration. Previous reports described AEC interaction with immune cells (B and T) promoting anti-inflammatory phenotypes, such as regulatory T cells.</div></div><div><h3>Methodology</h3><div>Now, we investigated AEC effects on macrophages and NK cells. Since AEC therapeutic potential is not mediated by intact cells only, we tested the ability of AEC secretome (AES) to modulate NK and macrophage proliferation, phenotype and functions.</div></div><div><h3>Results</h3><div>The amount of NK cells was reduced in the presence of AES. The expression of CD57, NKG2C, CD16, and TIGIT was downregulated, whereas the expression of NKG2A, NKp30, NKp46, and NKp44 increased. FACS analysis of surface CD107a expression revealed NK cell cytotoxicity increased (from 12.9% to 27.8%) upon exposure to AES., and cytotoxicity towards K562 cells (26.9%) increased almost 3-fold (73.7%).</div><div>Similarly, M2 macrophages increased in a dose-dependent manner. However, such effect was mainly mediated by soluble factors, such as M-CSF, and the vesicular component (AEC-derived EVs) failed to induce M2 polarisation. The extracellular vesicles and proteins released by primary human AECs were quantified by targeted proximity extension assay and several protein of interest, such as VEGF, IL-12B, or M-CSF, were found constitutively expressed, even in hypoxic conditions.</div></div><div><h3>Conclusion</h3><div>Our preliminary results suggested that secretome of AEC may drive the generation of NK cells with decreased proliferative ability and expression of senescence/exhaustion markers (CD57, NKG2C and TIGIT) and increased cytotoxicity receptor expression (NKG2A, NKp30, NKp44 and NKp46). Accordingly, such NK cells are more cytotoxic against leukemia target cells.</div><div>Collectively, our findings support the allogeneic transplantation of human AEC and their active role in local immune regulation, particularly in medical conditions where macrophage response needs to be modulated and contained.</div><div>Based on these and largely described immunomodulatory effects on adaptive and innate immune cells, allogeneic AEC-based treatments without immunosuppressants are legitimate, as well as novel cyto-therapeutic strategies for inflammatory disorders and auto-immune conditions.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 5","pages":"Pages S40-S41"},"PeriodicalIF":3.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888228","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":"Do Maternal and Fetal Demographics Affect the Quality of Umbilical Cord-Derived MSCs? Insights from a Colombian Cohort","authors":"A. Bedoya ,&nbsp;W. Jaraba-Alvarez ,&nbsp;Y. Blanquiceth ,&nbsp;J.P. Franco ,&nbsp;S. Ortiz ,&nbsp;V. Sánchez-Giraldo ,&nbsp;K. Halpert-Correa ,&nbsp;H. Ortega-Arellano ,&nbsp;C. Quintero-Gil","doi":"10.1016/j.jcyt.2025.03.097","DOIUrl":"10.1016/j.jcyt.2025.03.097","url":null,"abstract":"<div><h3>Background &amp; Aim</h3><div>Wharton's Jelly-derived mesenchymal stem cells (WJ-MSCs) have demonstrated regenerative and immunomodulatory properties. However, the influence of maternal and fetal demographics on WJ-MSC quality remains underexplored. Identifying correlations between maternal age, gestational parameters, and fetal characteristics could establish benchmarks for optimizing WJ-MSC isolation and application in clinical contexts. This study investigated correlations between demographic factors and WJ-MSC quality attributes.</div></div><div><h3>Methodology</h3><div>A retrospective analysis was conducted on WJ-MSCs isolated and characterized per ISCT guidelines. Umbilical cords (UCs) were collected from donors who provided informed consent for biobanking between April 2023 and April 2024. From 28 UCs yielding 48 cell lots, at least one line per cord was randomly analyzed. Data included maternal age, gestational age, parity, and neonatal metrics (weight, length). Infectious disease screenings were conducted on donor medical records and cord blood samples. WJ-MSCs were cultured under normoxic or hypoxic conditions, with quality assessments (P2–P4) including karyotype analysis, flow cytometry for ISCT markers (CD73, CD90, CD105, CD44), viability assays, differentiation potential (adipogenic, chondrogenic, osteogenic), and morphological evaluation. Correlations between demographics and MSC quality attributes were statistically analyzed using Jamovi 2.3.28.</div></div><div><h3>Results</h3><div>Of 28 UCs collected, 4 were excluded (2 due to infectious disease panel abnormalities, 2 due to contamination). Exclusions showed no correlation with membrane rupture times or other parameters. Mean maternal age was 25.1 years, with median gestational age of 39.1 weeks. All WJ-MSC lines met ISCT's criteria for MSC identity and sterility. Preliminary findings suggested a correlation between time from membrane rupture to delivery and expression levels of CD90, CD105, and CD73. A statistically significant difference in CD73 and CD90 expression variance was observed between male and female neonates, with smaller intervals in females. No significant correlation was identified between proliferation and demographic factors.</div></div><div><h3>Conclusion</h3><div>Preliminary data indicate that maternal and fetal demographics, particularly time from membrane rupture to delivery, influence specific marker expressions in WJ-MSCs. Markers also exhibit sex-specific differences. Further studies with larger samples and functionality testing are needed to validate findings and establish population-specific WJ-MSC standards.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 5","pages":"Page S57"},"PeriodicalIF":3.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887597","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":"From Donor to Therapy: How Robust Manufacturing Shapes the TCR repertoire and Cytotoxic Power of Donor-Derived Allogeneic ex vivo Expanded and Activated γδ T Cell Products","authors":"M.A. ter Haak ,&nbsp;C.C. Lucas ,&nbsp;B.B. Weekley ,&nbsp;G. Chen ,&nbsp;W. Pan ,&nbsp;D. Weber ,&nbsp;M. Bryne-Steele ,&nbsp;L. Lamb ,&nbsp;K.M. Rochlin","doi":"10.1016/j.jcyt.2025.03.071","DOIUrl":"10.1016/j.jcyt.2025.03.071","url":null,"abstract":"<div><h3>Background &amp; Aim</h3><div>Gamma-delta (γδ) T cell levels have been shown to positively correlate with Oncology outcomes. (γδ) T cells do not initiate GvHD and kill cancer via multiple innate ligands. A clinical trial (NCT03533816) is examining if a single infusion of donor-derived allogeneic ex vivo expanded and activated γδ T cells (EAGD) improves outcomes for leukemia patients undergoing haploidentical BMT with reduced intensity conditioning. The manufacturing for γδ T cells may require long processing &gt; 10 days. To understand the impact on the manufactured cells, the starting material and final product were analyzed to identify changes in cell activation, potency and function.</div></div><div><h3>Methodology</h3><div>This study includes analysis of a subset of EAGD products used in the INB-100 Phase 1 trial, manufactured from donors using a proprietary protocol. The starting material and final infused clinical product were analyzed for TCR repertoire and gene expression.</div></div><div><h3>Results</h3><div>The manufacturing shifted the TCR repertoire from αβ-TCR to γδ-TCR expression, with preferential expansion of Vγ9 clones. The diversity of αβ-TCR clones was significantly reduced, p &lt; 0.01, in the final product, while γδ-TCR diversity remained similar. Gene expression analysis revealed consistent upregulation of cellular markers of cytotoxicity (eg. INFG, GZMB, PRF1), activation, and immune cell trafficking/stimulation. Expression profiles were consistent across products, demonstrating robustness and reproducibility of the manufacturing.</div><div>The initial cohorts are fully enrolled, an expansion of up to 15 additional patients is being actively recruited and treated at dose level 2, the recommended phase 2 dose (RP2D). All patients in the initial 10 patient cohort passed one year without relapse, to-date no AML patients have relapsed with median OS of 23.3 as of Jan 17, 2024, with a manageable safety profile. Notably, circulating γδ T cell expansion and persistence of up to 1 year was observed, suggesting prolonged γδ T cell effector durability.</div></div><div><h3>Conclusion</h3><div>The proprietary manufacturing generates consistent robust and cytotoxic γδ T cell products with similar gene expression shifts from different donors. The clinical products exhibit, at the gene expression level, cytotoxicity, immune recruitment, and tissue trafficking capabilities. Subjects infused with EAGD product show durable relapse-free survival, comparing favorably with the ∼50% expected 1-year relapse-free survival for HaploCy BMT, suggesting they may have improved outcomes with gamma-delta T cells post-transplant.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 5","pages":"Page S44"},"PeriodicalIF":3.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888006","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":"Engineering Next-Generation Mesothelin CAR-T cells by Harnessing Naïve and Early Memory T cells","authors":"H.W. Song ,&nbsp;A. Venugopalan ,&nbsp;M. Prochazkova ,&nbsp;S. Sarkar ,&nbsp;P. Jin ,&nbsp;R.P. Somerville ,&nbsp;D. Stroncek ,&nbsp;R. Hassan ,&nbsp;S.L. Highfill","doi":"10.1016/j.jcyt.2025.03.063","DOIUrl":"10.1016/j.jcyt.2025.03.063","url":null,"abstract":"<div><h3>Background &amp; Aim</h3><div>CAR-T cells for the treatment of patients with solid tumors, including mesothelin CAR-Ts targeting mesothelioma, have shown limited clinical efficacy to date. It is hypothesized that one barrier to response is lack of T cell persistence, a quality associated with naïve and early memory T-cells. We therefore designed a GMP process to manufacture mesothelin CAR-Ts directly from these minimally differentiated T cells. CD62L is expressed on naïve, stem/central memory, and central memory T-cells but is also expressed on monocytes and B cells. Because monocytes can inhibit transduction and expansion, we depleted CD14⁺ monocytes prior to CD62L enrichment using a two-step magnetic selection.</div></div><div><h3>Methodology</h3><div>A total of 4 mononuclear cell (MNC) apheresis products from healthy donors were incubated with CD14 magnetic beads on the Sepax C-Pro, depleted for CD14⁺ monocytes on the CliniMACS Plus, and enriched for CD62L⁺ cells on the CliniMACS Prodigy. T-cells were activated using TransAct stimulation reagent plus IL-2, IL-7, and IL-15, followed by lentiviral transduction with a CAR expressing a novel scFv (hYP218) targeting the membrane-proximal domain of mesothelin. Cells were expanded on the CliniMACS Prodigy for 7-9 days, with a target harvest of day 7 for clinical products.</div></div><div><h3>Results</h3><div>Using the two-step magnetic selection process, we purified CD62L⁺ cells from an initial frequency of 54 - 76% CD62L⁺ of CD3⁺ to ≥99% CD62L⁺ of CD3⁺ (98% of total), while also depleting ≥94% of CD14⁺ monocytes, demonstrating successful purification. From 8.8 ± 1.5 × 10⁹ total MNCs, we isolated 1.8 ± 0.5 × 10⁹ CD62L⁺CD3⁺ T-cells, recovering 58% of CD62L⁺CD3⁺ cells on average during enrichment. We next initiated 55 × 10⁶ T-cells into culture, which expanded to 2.2 ± 0.4 × 10⁹ cells by day 7. T-cell purity increased from 83.1 ± 4.1% CD3⁺ on day 0 to above 96% on day 7 with 40-60% transduction at MOI=3.4. Approximately 98% of transduced T-cells expressed CD62L at harvest, suggesting that the naïve/early memory phenotype is maintained.</div></div><div><h3>Conclusion</h3><div>This innovative manufacturing process for generating mesothelin CAR-T cells demonstrates consistency and robustness, yielding a final product enriched with CD62L⁺ T cells, high transduction efficiency, and full compliance with all safety release criteria. This process will be utilized in a Phase 1 dose escalation study of patients with mesothelin-expressing tumors including mesothelioma as well as lung, thymic, colorectal, pancreatic, and gastric cancers.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 5","pages":"Pages S38-S39"},"PeriodicalIF":3.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888033","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":"Backgrounded Membrane Microscopy, a novel technique for the determination of contaminating particles in cell therapy products.","authors":"P. Dyer ,&nbsp;D. Khachadourian ,&nbsp;K. White ,&nbsp;B. Cordovez","doi":"10.1016/j.jcyt.2025.03.030","DOIUrl":"10.1016/j.jcyt.2025.03.030","url":null,"abstract":"<div><h3>Background &amp; Aim</h3><div>Distinguishing between different subvisible particle (SVP) species within a cell therapy product has proven challenging using standard techniques such as flow cytometry. This is in part due to the cell therapy product itself contributing to the subvisible particle population. This has been exemplified by the recent FDA issuance of a Form 483 concerning particle contamination in Kymriah® with wood, cellulose, brass, and steel, attributed to the cryopreservation bags. This has highlighted a need for a new approach in the determination of sub-visible particles within cell therapies.</div></div><div><h3>Methodology</h3><div>The combination of Backgrounded Membrane Imaging (BMI) and Side Illumination Membrane Imaging (SIMI), a form of darkfield microscopy, provides unique and definitive insights into the nature of different particle species. The presence of biological and non-biological (plastic, wood, metal) particles can be identified and counted using this combination of imaging approaches. Non-biological materials exhibit a strong SIMI signature when compared to biological matter, due in part to the relative refractive index and rigidity when examined on a filter membrane.</div></div><div><h3>Results</h3><div>Here in, we demonstrate the utility of the combined imaging modes for the identification of different non-biological materials mixed with CAR T cells at two loaded volumes 40uL and 400uL using a 96-well plate and 24-well white membrane plate, respectively.</div><div>The specific determination of biological matter, be it protein, DNA or lipid, is facile when stained with appropriate fluorescent dyes on a 96-well black membrane plate. The specific determination of biological matter, be it protein, DNA or lipid, is facile when stained with appropriate fluorescent dyes on black membrane plates.</div></div><div><h3>Conclusion</h3><div>This approach provides additional utility for the identification of protein aggregates, cell clumps, cell-bound microspheres, viable cell populations within a rapid high-throughput assay.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 5","pages":"Page S22"},"PeriodicalIF":3.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888109","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":"Addressing Gaps in Pharmacy Standards for Cell and Gene Therapy Management","authors":"J. Wren ,&nbsp;L. Barnes ,&nbsp;C. Bocquet ,&nbsp;S. Rajbhandary","doi":"10.1016/j.jcyt.2025.03.035","DOIUrl":"10.1016/j.jcyt.2025.03.035","url":null,"abstract":"<div><h3>Background and Aims</h3><div>The rapid growth of FDA-approved cell and gene therapies (CGTs) has elevated the role of pharmacies in the receipt, storage, handling, and dispensing of these complex and high-value treatments. While pharmacies play a critical role in safeguarding CGT integrity and ensuring patient safety, current pharmacy quality standards and accreditations are less suited to the specialized requirements for managing CGTs. This gap underscores the urgent need for CGT-specific standards to ensure product potency and integrity, operational consistency, and patient safety.</div><div>To address this gap, a multidisciplinary committee of pharmacy stakeholders convened to develop the 1st edition of the Cell and Gene Therapy Standards for Pharmacy (see Figure 1 for committee composition and expertise). These Standards, grounded in established quality system essentials, aim to guide the safe and consistent management of CGTs across various pharmacy settings.</div></div><div><h3>Methodology</h3><div>To further identify existing gaps and future needs, a targeted survey of pharmacy stakeholders (n = 10) was conducted. Although the sample size was limited, the qualitative feedback provided valuable insights into current practices and areas requiring improvement (see Figure 2 for full survey results).</div></div><div><h3>Results</h3><div>1. Growing Role of Pharmacies:</div><div>Nearly all respondents (90% strongly agreed, 10% agreed) anticipate that pharmacies will assume an increasingly critical role in dispensing FDA-approved CGTs over the next 3–5 years. This expectation underscores the importance of readiness, training, and infrastructure support.</div><div>2. Need for Enhanced Standards:</div><div>Only half of the respondents felt that existing standards are adequate for managing CGTs, while 40% disagreed or strongly disagreed. This finding affirms the urgent need to establish and implement updated, specialized guidelines that address the unique handling, receipt, storage, and dispensing requirements of CGTs.</div></div><div><h3>Conclusion</h3><div>These findings reinforce the necessity of developing robust, CGT-specific standards for pharmacy practice. By proactively establishing these standards, pharmacies can better mitigate risks, uphold product integrity, and ensure patient safety—ultimately equipping themselves with tools to safeguard quality, and enhance patient outcomes.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 5","pages":"Pages S24-S25"},"PeriodicalIF":3.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888114","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)00077-5","DOIUrl":"10.1016/S1465-3249(25)00077-5","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 4","pages":"Page A5"},"PeriodicalIF":3.7,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143682266","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)00074-X","DOIUrl":"10.1016/S1465-3249(25)00074-X","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 4","pages":"Page A1"},"PeriodicalIF":3.7,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143682263","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}