CytotherapyPub Date : 2024-06-01DOI: 10.1016/j.jcyt.2024.03.196
X. Liu, A. Rivera, A. Pepper, M. Maffie, C. Bertagnolli, T. Shook, L. Gordon, S. Singhal, J. Mehta, F. Zhu
{"title":"STABILITY PROGRAM REVALIDATION AND OPTIMIZATION, ONE CENTER EXPERIENCE**","authors":"X. Liu, A. Rivera, A. Pepper, M. Maffie, C. Bertagnolli, T. Shook, L. Gordon, S. Singhal, J. Mehta, F. Zhu","doi":"10.1016/j.jcyt.2024.03.196","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.03.196","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141278613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CytotherapyPub Date : 2024-06-01DOI: 10.1016/j.jcyt.2024.06.002
Ashish O. Gupta, Melissa Azul, S. Bhoopalan, Allistair Abraham, A. Bertaina, Alan Bidgoli, Carmem Bonfim, Amy DeZern, Jingjing Li, C. Louis, Duncan Purtill, Annalisa Ruggeri, J. J. Boelens, S. Prockop, Akshay Sharma
{"title":"International Society for Cell & Gene Therapy Stem Cell Engineering Committee report on the current state of hematopoietic stem and progenitor cell–based genomic therapies and the challenges faced","authors":"Ashish O. Gupta, Melissa Azul, S. Bhoopalan, Allistair Abraham, A. Bertaina, Alan Bidgoli, Carmem Bonfim, Amy DeZern, Jingjing Li, C. Louis, Duncan Purtill, Annalisa Ruggeri, J. J. Boelens, S. Prockop, Akshay Sharma","doi":"10.1016/j.jcyt.2024.06.002","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.06.002","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141392884","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}
CytotherapyPub Date : 2024-06-01DOI: 10.1016/j.jcyt.2024.05.022
Marinna Madrid, U. Lakshmipathy, Xiaokui Zhang, K. Bharti, Dominic M. Wall, Yoji Sato, G.F. Muschler, Anthony Ting, N. Smith, Shuhei Deguchi, Shin Kawamata, Jennifer C. Moore, Bar Makovoz, Stephen Sullivan, Veronica Falco, A. Al‐Riyami
{"title":"Considerations for the development of iPSC-derived cell therapies: A review of key challenges by the JSRM-ISCT iPSC Committee","authors":"Marinna Madrid, U. Lakshmipathy, Xiaokui Zhang, K. Bharti, Dominic M. Wall, Yoji Sato, G.F. Muschler, Anthony Ting, N. Smith, Shuhei Deguchi, Shin Kawamata, Jennifer C. Moore, Bar Makovoz, Stephen Sullivan, Veronica Falco, A. Al‐Riyami","doi":"10.1016/j.jcyt.2024.05.022","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.05.022","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141393461","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}
CytotherapyPub Date : 2024-06-01DOI: 10.1016/j.jcyt.2024.03.439
T. Okazaki
{"title":"GMP COMPLIANT MANUFACTURING PROCESS DEVELOPMENT OF ONCOLYTIC VIROTHERAPY","authors":"T. Okazaki","doi":"10.1016/j.jcyt.2024.03.439","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.03.439","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141277137","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}
CytotherapyPub Date : 2024-06-01DOI: 10.1016/j.jcyt.2024.06.008
J. Tanna, Chase D McCann, Rhonda Smith, Adriana Pitino, Almaz Asgedom, Srey Leap Kong, You Lian Weiner, Kathryn Bushnell, Jennifer Webb, Patrick J. Hanley
{"title":"Environmental Monitoring of cGMP Cleanroom Facilities for Manufacturing of Cellular Therapy Products in an Academic Hospital Setting","authors":"J. Tanna, Chase D McCann, Rhonda Smith, Adriana Pitino, Almaz Asgedom, Srey Leap Kong, You Lian Weiner, Kathryn Bushnell, Jennifer Webb, Patrick J. Hanley","doi":"10.1016/j.jcyt.2024.06.008","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.06.008","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141402667","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}
CytotherapyPub Date : 2024-06-01DOI: 10.1016/j.jcyt.2024.06.001
Alison Felipe Bordini Biggi, R. N. Silvestre, Mariane Cariati Tirapelle, J.T. de Azevedo, Henry David Mogollón García, Matheus Henrique dos Santos, S. C. G. de Lima, L. E. B. de Souza, D. Covas, K. Malmegrim, Marxa L. Figueiredo, V. Picanço-Castro
{"title":"IL-27 Engineered CAR.19-NK-92 Cells Exhibit Enhanced Therapeutic Efficacy","authors":"Alison Felipe Bordini Biggi, R. N. Silvestre, Mariane Cariati Tirapelle, J.T. de Azevedo, Henry David Mogollón García, Matheus Henrique dos Santos, S. C. G. de Lima, L. E. B. de Souza, D. Covas, K. Malmegrim, Marxa L. Figueiredo, V. Picanço-Castro","doi":"10.1016/j.jcyt.2024.06.001","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.06.001","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141402242","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":"Enhanced anti-tumor activity mediated by combination chimeric antigen receptor T cells targeting GD2 and GPC2 in high-risk neuroblastoma.","authors":"Huantong Wu, Guangji Zhang, Zhongfeng Liu, Weihua Liu, Xuan Wang, Yu Zhao","doi":"10.1016/j.jcyt.2024.05.023","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.05.023","url":null,"abstract":"<p><strong>Background aims: </strong>Chimeric antigen receptor T (CAR-T) cells targeting single antigens show limited activity against solid tumors due to poor T cell persistence, low efficiency infiltration, and exhaustion together with heterogeneous tumor-associated antigen (TAA) expression. This is also true in high-risk neuroblastoma (HRNB), a lethal pediatric extracranial malignancy. To overcome these obstacles, a combinational strategy using GD2-specific and GPC2-specific CAR-T cells was developed to improve immunotherapeutic efficacy.</p><p><strong>Methods: </strong>We individually developed GD2-specific and GPC2-specific CARs containing a selective domain (sCAR) which was a peptide of 10 amino acids derived from human nuclear autoantigen La/SS-B. These constructs allowed us to generate two different HRNB antigen-specific CAR-T cells with enhanced biological activity through stimulating sCAR-engrafted T cells via a selective domain-specific monoclonal antibody (SmAb). Binding affinity and stimulation of GD2- and GPC2-specific sCARs by SmAb were measured, and transient and persistent anti-tumor cytotoxicity of GD2sCAR-T and GPC2sCAR-T cells were quantified in neuroblastoma cell lines expressing different TAA levels. The anti-tumor pharmaceutical effects and cellular mechanisms mediated by single or combinational sCAR-T cells were evaluated in vitro and in vivo.</p><p><strong>Results: </strong>GD2- and GPC2-specific sCARs had antigen-specific binding affinity similar to their parental counterparts and were recognized by SmAb. SmAb-mediated stimulation selectively activated sCAR-T proliferation and increased central memory T cells in the final products. SmAb-stimulated sCAR-T cells had enhanced transient cytolytic activity, and combination therapy extended long-term anti-tumor activity in vitro through TNF-α and IL-15 release. Stimulated sCAR-T cells overcame heterogeneous antigen expression in HRNB, and the multi-TAA-targeting strategy was especially efficacious in vivo, inducing apoptosis through the caspase-3/PARP pathway and inhibiting the release of several tumor-promoting cytokines.</p><p><strong>Conclusions: </strong>These data suggest that combined targeting of multiple TAAs is a promising strategy to overcome heterogenous antigen expression in solid tumors and extend CAR-T cell persistence for HRNB immunotherapy.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141433242","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}
CytotherapyPub Date : 2024-05-31DOI: 10.1016/j.jcyt.2024.05.020
Pedro Silva Couto, Dale J Stibbs, Marco C Rotondi, Rana Khalife, Dennis Wolf, Yasuhiro Takeuchi, Qasim A Rafiq
{"title":"Biological differences between adult and perinatal human mesenchymal stromal cells and their impact on the manufacturing processes.","authors":"Pedro Silva Couto, Dale J Stibbs, Marco C Rotondi, Rana Khalife, Dennis Wolf, Yasuhiro Takeuchi, Qasim A Rafiq","doi":"10.1016/j.jcyt.2024.05.020","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.05.020","url":null,"abstract":"<p><p>The biological properties of human mesenchymal stromal cells (hMSCs) have been explored in over a thousand clinical trials in the last decade. Although hMSCs can be isolated from multiple sources, the degree of biological similarity between cell populations from these sources remains to be determined. A comparative study was performed investigating the growth kinetics and functionality of hMSCs isolated from adipose tissue (AT), bone marrow (BM) and umbilical cord tissue (UCT) expanded in monolayer over five passages. Adult hMSCs (AT, BM) had a slower proliferation ability than the UCT-hMSCs, with no apparent differences in their glucose consumption profile. BM-hMSCs produced higher concentrations of endogenous vascular endothelial growth factor (VEGF) compared to AT- and UCT-hMSCs. This study also revealed that UCT-hMSCs were more efficiently transduced by a lentiviral vector carrying a VEGF gene than their adult counterparts. Following cellular immunophenotypic characterization, no differences across the sources were found in the expression levels of the typical markers used to identify hMSCs. This work established a systematic approach for cell source selection depending on the hMSC's intended clinical application.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141545504","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}
CytotherapyPub Date : 2024-05-31DOI: 10.1016/j.jcyt.2024.05.024
Hannah W Song, Jennifer N Solomon, Fernanda Masri, Amanda Mack, Nisha Durand, Emmanuelle Cameau, Noushin Dianat, Arwen Hunter, Steve Oh, Brianna Schoen, Matthew Marsh, Christopher Bravery, Cenk Sumen, Dominic Clarke, Kapil Bharti, Julie G Allickson, Uma Lakshmipathy
{"title":"Bioprocessing considerations for generation of iPSCs intended for clinical application: perspectives from the ISCT Emerging Regenerative Medicine Technology working group.","authors":"Hannah W Song, Jennifer N Solomon, Fernanda Masri, Amanda Mack, Nisha Durand, Emmanuelle Cameau, Noushin Dianat, Arwen Hunter, Steve Oh, Brianna Schoen, Matthew Marsh, Christopher Bravery, Cenk Sumen, Dominic Clarke, Kapil Bharti, Julie G Allickson, Uma Lakshmipathy","doi":"10.1016/j.jcyt.2024.05.024","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.05.024","url":null,"abstract":"<p><p>Approval of induced pluripotent stem cells (iPSCs) for the manufacture of cell therapies to support clinical trials is now becoming realized after 20 years of research and development. In 2022 the International Society for Cell and Gene Therapy (ISCT) established a Working Group on Emerging Regenerative Medicine Technologies, an area in which iPSCs-derived technologies are expected to play a key role. In this article, the Working Group surveys the steps that an end user should consider when generating iPSCs that are stable, well-characterised, pluripotent, and suitable for making differentiated cell types for allogeneic or autologous cell therapies. The objective is to provide the reader with a holistic view of how to achieve high-quality iPSCs from selection of the starting material through to cell banking. Key considerations include: (i) intellectual property licenses; (ii) selection of the raw materials and cell sources for creating iPSC intermediates and master cell banks; (iii) regulatory considerations for reprogramming methods; (iv) options for expansion in 2D vs. 3D cultures; and (v) available technologies and equipment for harvesting, washing, concentration, filling, cryopreservation, and storage. Some key process limitations are highlighted to help drive further improvement and innovation, and includes recommendations to close and automate current open and manual processes.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141545505","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}
CytotherapyPub Date : 2024-05-26DOI: 10.1016/j.jcyt.2024.05.021
Lei Deng, Xiaolin Yu, Xiaocheng Song, Rui Guan, Wenjun Li, Yixi Hou, Yan Shao, Yuerong Zhao, Jing Wang, Yue Liu, Qianqian Xiao, Bo Xin, Fang Zhou
{"title":"Efficacy and risk of donor-derived CAR-T treatment of relapsed B-cell acute lymphoblastic leukemia after hematopoietic stem cell transplantation.","authors":"Lei Deng, Xiaolin Yu, Xiaocheng Song, Rui Guan, Wenjun Li, Yixi Hou, Yan Shao, Yuerong Zhao, Jing Wang, Yue Liu, Qianqian Xiao, Bo Xin, Fang Zhou","doi":"10.1016/j.jcyt.2024.05.021","DOIUrl":"https://doi.org/10.1016/j.jcyt.2024.05.021","url":null,"abstract":"<p><p>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, P = 0.017) and platelet recovery at 30 days (HR 6.807, 95% CI 1.61-28.83, P = 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.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":null,"pages":null},"PeriodicalIF":4.5,"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}