Cytotherapy最新文献

{"title":"Expansion of tumor-infiltrating and marrow-infiltrating lymphocytes from pediatric malignant solid tumors.","authors":"Jonathan Metts, Madeline Rodriguez-Valentin, Jonathan Hensel, Alex Alfaro, Christopher W Snyder, Odion Binitie, Caroline Chebli, Hector Monforte, Shari Pilon-Thomas, John Mullinax","doi":"10.1016/j.jcyt.2024.08.002","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.08.002","url":null,"abstract":"<p><strong>Introduction: </strong>The expansion of tumor-infiltrating lymphocytes (TIL) for adoptive cellular therapy is under investigation in many solid tumors of adulthood. Marrow-infiltrating lymphocytes (MIL) have demonstrated antitumor reactivity preclinically. Successful expansion of TIL/MIL has not been reported across pediatric solid tumor histologies. The objective of this study was to demonstrate successful expansion of TIL from pediatric solid tumors for translation in an adoptive cell therapy (ACT) treatment strategy.</p><p><strong>Methods: </strong>A prospective study of TIL/MIL expansion was performed on solid tumors of pediatric patients undergoing standard-of-care procedures. TIL/MIL expansions were performed in the presence of high-dose interleukin 2. To demonstrate a full-scale expansion to clinically-relevant cell doses for TIL therapy, initial TIL culture was followed by a rapid expansion protocol for select patients. Expanded specimens were analyzed for phenotype by flow cytometry and for anti-tumor reactivity by the interferon-gamma release assay.</p><p><strong>Results: </strong>Eighteen tumor samples were obtained. Initial TIL cultures were successfully generated from 14/18 samples (77.7%). A median of 5.52 × 107 (range: 2.5 × 106-3.23 × 108) cells were produced from initial cultures, with 46.9% expressing a CD3 phenotype (46.9%). Eight samples underwent rapid expansion, demonstrating a median 458-fold expansion and a CD3 phenotype of 98%. Initial MIL cultures were successfully generated from five samples, with a predominantly CD3 phenotype (45.2%). Sufficient tumor tissue was only available for seven TIL samples to be tested for reactivity; none demonstrated responsiveness to autologous tumor.</p><p><strong>Conclusions: </strong>TIL and MIL expansion from pediatric solid tumors was successful, including the full-scale expansion process. This data supports translation to an ACT-TIL treatment strategy in the pediatric population and thus a Phase I trial of ACT-TIL in pediatric high-risk solid tumors is planned.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146763","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":"CD19-chimeric antigen receptor-invariant natural killer T cells transactivate NK cells and reduce alloreactivity","authors":"Anton Wesle, Emmanuelle Moraes Ribeiro, Rebekka Schairer, Hildegard Keppeler, Fulya Korkmaz, Pia Radszuweit, Kristin Bieber, Claudia Lengerke, Dominik Schneidawind, Corina Schneidawind","doi":"10.1016/j.jcyt.2024.08.004","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.08.004","url":null,"abstract":"Invariant natural killer T (iNKT) cells are a small fraction of T lymphocytes with strong cytotoxic and immunoregulatory properties. We previously showed that human culture-expanded iNKT cells prevent alloreactivity and lyse primary leukemia blasts. Here, iNKT cells have several advantages over T cells based on their immunoregulatory capabilities. Since chimeric antigen receptors (CARs) increase the benefit of immune effector cells, they play a crucial role in improvement of cytotoxic abilities of novel cellular therapeutics such as iNKT cells. In the present study, we investigated transactivation of NK cells and prevention of alloreactivity through iNKT cells transduced with a CD19-directed CAR. iNKT cells were isolated by magnetic cell separation from peripheral blood mononuclear cells and transduced with a CD19-CAR retrovirus. Transduction efficiency, purity and cell subsets were measured by flow cytometry. Transactivation and cytotoxicity assays have been established to investigate the ability of CD19-CAR-iNKT cells to transactivate primary NK cells. A mixed lymphocyte reaction (MLR) was performed to explore the inhibition of alloreactive CD3+ T cells by CD19-CAR-iNKT cells. CD19-CAR-iNKT cells are able to transactivate NK cells independent of cell contact: The expression of activation marker CD69 was significantly increased and also production of the proinflammatory cytokine interferon-gamma was higher in NK cells pretreated with CD19-CAR-iNKT cells. Consequently, the cytotoxic activity of such NK cells was significantly increased being able to lyse leukemia cells more effectively than without prior transactivation. Adding CD19-CAR-iNKT cells to an MLR resulted in a decreased expression of the T cell activation marker CD25 on alloreactive CD3+ T lymphocytes stimulated with HLA mismatched dendritic cells. Also, the proliferation of alloreactive CD3+ T lymphocytes was significantly reduced in this setting. We demonstrate that CD19-CAR-iNKT cells keep their immunoregulatory properties despite transduction with a CAR making them an attractive effector cell population for application after allogeneic hematopoietic cell transplantation. By transactivating NK cells, increasing their cytotoxic activity and suppressing alloreactive T cells, they might further improve outcomes through prevention of both relapse and graft-versus-host disease.","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248123","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":"Advancing immunomodulatory functions in mesenchymal stem/stromal cells through targeting the GATA6-mediated pathway.","authors":"Eric Chang-Yi Lin, Madison P Davis, Ming-Song Lee, Gui Ma, Wei Xu, Yuan-I Chang, Wan-Ju Li","doi":"10.1016/j.jcyt.2024.08.001","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.08.001","url":null,"abstract":"<p><strong>Background aims: </strong>The immunomodulatory capacity of mesenchymal stem/stromal cells (MSCs) is a key feature that makes them particularly valuable for regenerative medicine. However, this potential is affected by the chronological aging of the donors and the cell expansion procedures in culture. We have demonstrated that GATA binding protein 6 (GATA6) plays a pivotal role in the aging of MSCs and inhibiting GATA6 rejuvenates the characteristics of MSCs.</p><p><strong>Methods: </strong>In this study, we compared the immunomodulatory capabilities of young and old MSC models, using induced pluripotent stem cells-derived rejuvenated MSCs (rMSCs) and their parental MSCs (pMSCs), respectively, to identify a key mechanism involved in the differential regulation of these capabilities. Additionally, we explored the role of GATA6 in mediating the mechanism.</p><p><strong>Results: </strong>Our results demonstrated that rMSCs exhibited downregulated aging-associated regulators, including p53, p21 and GATA6, and showed enhanced suppression of T cell proliferation compared to pMSCs. Through analyzing our previous RNA-seq data and employing target gene knockdown, we determined both suppressors of cytokine signaling 3 (SOCS3) and interleukin 6 were involved in GATA6-induced regulation, collectively affecting the expression of programmed death ligand 1 (PDL1) in both pMSCs and rMSCs.</p><p><strong>Conclusions: </strong>Our findings underline the significance of the GATA6/SOCS3/PDL1 pathway in regulating aging-associated changes in MSC immunomodulatory activity, providing valuable insights into the potential use of rMSCs in the treatment of immune diseases and regenerative medicine.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142114410","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":"Enhancing photodynamic and radionuclide therapy by small interfering RNA (siRNA)-RAD51 transfection via self-emulsifying delivery systems (SNEDDS).","authors":"Ulises Paredes-Hernández, Leslie V Aguilar-Peña, Keila Isaac-Olivé, Blanca Ocampo-García, Irazú Contreras, José A Estrada, Germán Izquierdo, Enrique Morales-Avila, Liliana Aranda-Lara","doi":"10.1016/j.jcyt.2024.08.003","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.08.003","url":null,"abstract":"<p><strong>Background aims: </strong>Gene-silencing by small interfering RNA (siRNA) is an attractive therapy to regulate cancer death, tumor recurrence or metastasis. Because siRNAs are easily degraded, it is necessary to develop transport and delivery systems to achieve efficient tumor targeting. Self-nanoemulsifying systems (SNEDDS) have been successfully used for pDNA transport and delivery, so they may be useful for siRNA. The aim of this work is to introduce siRNA-RAD51 into a SNEDDS prepared with Phospholipon-90G, Labrafil-M1944-CS and Cremophor-RH40 and evaluate its efficacy in preventing homologous recombination of DNA double-strand breaks caused by photodynamic therapy (PDT) and ionizing radiation (IR).</p><p><strong>Methods: </strong>The siRNA-RAD51 was loaded into SNEDDS using chitosan. Transfection capacity was estimated by comparison with Lipofectamine-2000.</p><p><strong>Results: </strong>SNEDDS(siRNA-RAD51) induced gene silencing effect on the therapies evaluated by cell viability and clonogenic assays using T47D breast cancer cells.</p><p><strong>Conclusions: </strong>SNEDDS(siRNA-RAD51) shown to be an effective siRNA-delivery system to decrease cellular resistance in PDT or IR.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057186","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":"Late-onset relapsing neurotoxicity after Brexucabtagene autoleucel associated with high chimeric antigen receptor T cells in cerebrospinal fluid.","authors":"Chiara De Philippis, Arianna Giacomel, Umberto Pensato, Chiara Pinton, Daniela Taurino, Daniele Mannina, Jacopo Mariotti, Barbara Sarina, Simona Marcheselli, Inna Timofeeva, Rossana Capizzuto, Armando Santoro, Stefania Bramanti","doi":"10.1016/j.jcyt.2024.07.015","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.07.015","url":null,"abstract":"<p><strong>Background aims: </strong>Mounting evidence suggests that persistent cell expansion is the main driver for both efficacy and toxicity of chimeric antigen receptor (CAR) T-cell therapy. Hereby, we describe a case of delayed recurrent neurotoxicity associated with late CAR T-cells re-expansion.</p><p><strong>Case description: </strong>A 44-year-old man suffering from mantle cell lymphoma received brexu-cel. After infusion, he developed grade 2 cytokine release syndrome. On day +11, grade 3 neurotoxicity was reported and high-dose methylprednisolone was started with a complete resolution of neurological manifestations. On day +30, he experienced a late-onset CAR T-cell toxicity associated with CAR T-cell re-expansion. The patient was treated with tocilizumab and dexamethasone, with resolution of symptoms. On day +58, he was readmitted for new onset of neurotoxicity. Notably, a new CAR T-cell expansion was observed, with an unexpectedly elevated cerebrospinal fluid/blood ratio. The patient was promptly treated with dexamethasone and then escalated to high-dose methylprednisolone and anakinra, with resolution of his neurologic condition noted.</p><p><strong>Conclusions: </strong>CAR T-cell-related neurotoxicity usually has an early monophasic course. To our knowledge, this is the first case of late-onset, recurrent neurotoxicity. Moreover, an elevated level of cerebrospinal fluid CAR T cells was observed, which may suggest that the delayed neurotoxicity was primarily caused by the brain infiltration of CAR T cells rather than driven by cytokine-mediated neuroinflammation.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996870","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":"Handling the different requirements for commercial and investigational MNC collections by apheresis","authors":"","doi":"10.1016/j.jcyt.2024.04.001","DOIUrl":"10.1016/j.jcyt.2024.04.001","url":null,"abstract":"<div><h3>Background</h3><p>With the success of chimeric antigen receptor T-cell (CAR-T) and similar cellular-based therapies, the demand for collection of autologous mononuclear cells by apheresis (MNC(A)) from blood by apheresis has increased. From an apheresis technical standpoint, the collection of MNC(A) is relatively straightforward, especially when compared with collection of hematopoietic progenitor cells (HPC(A)). Most of the collection for MNC(A) are performed for the commercial entities, who use the product for manufacturing cellular therapeutics. We have noticed discrepancies in the handling and apheresis processes required by different companies in obtaining essentially the same product (all companies in the study manufacture CAR-T-based products). We have analyzed the MNC collection requirements from all FDA-approved CAR-T cellular products and some investigational products collected at University of Nebraska Medical Center. We identified discrepancies in the process and suggested mitigation strategies.</p></div><div><h3>Methods</h3><p>Step-by-step analysis of the collection requirements. Review of the current guidelines and recommendations on this issue.</p></div><div><h3>Results</h3><p>Multiple discrepancies in the collection process have been identified, even in the products collected for the same company. Practical approach of satisfying all the requirements based on University of Nebraska Medical Center experience has been suggested.</p></div><div><h3>Conclusion</h3><p>The current recommendations from multiple sources were reviewed in discussion.</p></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140783926","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":"Safety and potential efficacy of expanded mesenchymal stromal cells of bone marrow and umbilical cord origins in patients with chronic spinal cord injuries: a phase I/II study","authors":"","doi":"10.1016/j.jcyt.2024.03.480","DOIUrl":"10.1016/j.jcyt.2024.03.480","url":null,"abstract":"<div><h3>Background aims</h3><p>Spinal cord injury (SCI) affects patients' physical, psychological, and social well-being. Presently, treatment modalities for chronic SCI have restricted clinical effectiveness. Mesenchymal stromal cells (MSCs) demonstrate promise in addressing nervous tissue damage. This single-center, open-label, parallel-group randomized clinical trial aimed to assess the safety and efficacy of intraoperative perilesional administration of expanded autologous bone marrow-derived MSCs (BMMSCs), followed by monthly intrathecal injections, in comparison to monthly intrathecal administration of expanded allogeneic umbilical cord-derived MSCs (UCMSCs) for individuals with chronic SCI.</p></div><div><h3>Methods</h3><p>Twenty participants, who had a minimum of 1 year of SCI duration, were enrolled. Each participant in Group A received perilesional BMMSCs, followed by monthly intrathecal BMMSCs for three injections, while Group B received monthly intrathecal UCMSCs for three injections. Safety and efficacy were evaluated using the American Spinal Cord Injury Association (ASIA) score for at least 1 year post the final injection. Statistical analysis was conducted using the Wilcoxon signed-rank test.</p></div><div><h3>Results</h3><p>Group A comprised 11 participants, while Group B included 9. The mean follow-up duration was 22.65 months. Mild short-term adverse events encompassed headaches and back pain, with no instances of long-term adverse events. Both groups demonstrated significant improvements in total ASIA scores, with Group A displaying more pronounced motor improvements.</p></div><div><h3>Conclusions</h3><p>Our findings indicate that perilesional administration of expanded autologous BMMSCs, followed by monthly intrathecal BMMSCs for three injections, or monthly intrathecal UCMSCs for three injections appear to be safe and hold promise for individuals with chronic SCI. Nonetheless, larger-scale clinical trials are imperative to validate these observations.</p></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S146532492400570X/pdfft?md5=ff7c75d9293feb1e830f8c77dc7ba842&pid=1-s2.0-S146532492400570X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140794099","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":"Treatment of post-allogeneic hematopoietic stem cell transplant cytopenias with sequential doses of multipotent mesenchymal stromal/stem cells","authors":"","doi":"10.1016/j.jcyt.2024.04.006","DOIUrl":"10.1016/j.jcyt.2024.04.006","url":null,"abstract":"<div><h3>Background aims</h3><p>Cytopenias after allogeneic stem cell transplantation (allo-SCT) are a common complication, the underlying pathogenic mechanisms of which remain incompletely understood. Multipotent mesenchymal stromal/stem cell (MSC) therapy has been successfully employed in the treatment of immune-related disorders and can aid in the restoration of the hematopoietic niche.</p></div><div><h3>Methods</h3><p>A phase II clinical trial to assess the efficacy and safety of administering four sequential doses of ex-vivo expanded bone marrow MSCs from a third-party donor to patients with persistent severe cytopenias after allo-SCT was performed.</p></div><div><h3>Results</h3><p>The overall response rate on day 90 was 75% among the 27 evaluable patients (comprising 12 complete responses, 8 partial responses, and 7 with no response). The median time to respond was 14.5 days. Responses were observed across different profiles, including single or multiple affected lineages, primary or secondary timing, and potential immune-mediated or post-infectious pathophysiology versus idiopathic origin. With a median follow-up for surviving patients of 85 months after MSC infusion, 53% of patients are alive. Notably, no adverse events related to MSC therapy were reported.</p></div><div><h3>Conclusions</h3><p>In summary, the sequential infusion of third-party MSCs emerges as a viable and safe therapeutic option, exhibiting potential benefits for patients experiencing cytopenias following allo-SCT.</p></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1465324924006121/pdfft?md5=d7ea73847cb08b40fd42588729296794&pid=1-s2.0-S1465324924006121-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140784145","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":"Current guidelines, challenges and future recommendations for regulation of stem cell research and therapy: a commentary","authors":"","doi":"10.1016/j.jcyt.2024.04.076","DOIUrl":"10.1016/j.jcyt.2024.04.076","url":null,"abstract":"<div><p>In recent years, Malaysia has seen a surge in stem cell therapy for various medical conditions. However, the regulation of stem cell research and therapy in Malaysia faces several challenges such as the emergence of unregulated clinics and a lack of specific legislation. Some urgent measures, including enactment of specific laws, strengthened monitoring, as well as increased public awareness and education, are crucial. Therefore, stem cell therapy regulation requires concerted efforts by the policymakers, regulator bodies and healthcare professionals. This commentary discusses the current guidelines and challenges in Malaysian stem cell therapy regulation and proposes some future recommendations that could pave the way for responsible progress of stem cell research and therapy globally.</p></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141045663","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 platelet lysate enhances in vivo activity of CAR-Vδ2 T cells by reducing cellular senescence and apoptosis","authors":"","doi":"10.1016/j.jcyt.2024.03.006","DOIUrl":"10.1016/j.jcyt.2024.03.006","url":null,"abstract":"<div><h3>Background aims</h3><p>Vγ9Vδ2 T cells are an attractive cell platform for the off-the-shelf cancer immunotherapy as the result of their lack of alloreactivity and inherent multi-pronged cytotoxicity, which could be further amplified with chimeric antigen receptors (CARs). In this study, we sought to enhance the <em>in vivo</em> longevity of CAR-Vδ2 T cells by modulating <em>ex vivo</em> manufacturing conditions and selecting an optimal CAR costimulatory domain.</p></div><div><h3>Methods</h3><p>Specifically, we compared the anti-tumor activity of Vδ2 T cells expressing anti-CD19 CARs with costimulatory endodomains derived from CD28, 4-1BB or CD27 and generated in either standard fetal bovine serum (FBS)- or human platelet lysate (HPL)-supplemented medium.</p></div><div><h3>Results</h3><p>We found that HPL supported greater expansion of CAR-Vδ2 T cells with comparable <em>in vitro</em> cytotoxicity and cytokine secretion to FBS-expanded CAR-Vδ2 T cells. HPL-expanded CAR-Vδ2 T cells showed enhanced <em>in vivo</em> anti-tumor activity with longer T-cell persistence compared with FBS counterparts, with 4-1BB costimulated CAR showing the greatest activity. Mechanistically, HPL-expanded CAR Vδ2 T cells exhibited reduced apoptosis and senescence transcriptional pathways compared to FBS-expanded CAR-Vδ2 T cells and increased telomerase activity.</p></div><div><h3>Conclusions</h3><p>This study supports enhancement of therapeutic potency of CAR-Vδ2 T cells through a manufacturing improvement.</p></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1465324924000951/pdfft?md5=6a0a4066a5ed48c9747f78a3f38ad023&pid=1-s2.0-S1465324924000951-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140150317","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}