Lalitha Soundararajan, Harshini Surendran, Niharika Patlolla, Rajani Battu, Jonathan Stoddard, Sebastian Arrizabalaga, Zengping Liu, Gopal Lingam, Xinyi Su, Renee C Ryals, Rajarshi Pal
{"title":"大规模生产的同种异体RPE细胞悬浮液证明了临床前安全性和有效性，并获得了IND批准。","authors":"Lalitha Soundararajan, Harshini Surendran, Niharika Patlolla, Rajani Battu, Jonathan Stoddard, Sebastian Arrizabalaga, Zengping Liu, Gopal Lingam, Xinyi Su, Renee C Ryals, Rajarshi Pal","doi":"10.1038/s41536-025-00407-0","DOIUrl":null,"url":null,"abstract":"<p><p>Cell replacement therapy is a promising therapeutic option for dry age-related macular degeneration (AMD). In this study, we outline our design for scalable manufacture with appropriate quality gates and present in vivo data for establishing preclinical safety and efficacy of an induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) product, thus laying the foundation for Phase 1/2a trial approval in India (ClinicalTrials.gov ID: NCT06394232; date of registration: 23<sup>rd</sup> September 2024). Escalating doses of RPE cell suspension in immunocompromised animals demonstrated absence of tumor formation up to 9 months post-injection. Good Laboratory Practices (GLP) toxicology and tolerability studies in rabbits and non-human primates (NHP) respectively showed no major adverse events. RPE transplanted into immune suppressed RCS rats showed integration, neuroprotection and rescue of visual function. In addition, we provide a detailed description of the modifications in GMP manufacturing protocol to create a final product with a unique composition and Chemistry, Manufacturing and Controls (CMC) studies performed during product development.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"10 1","pages":"19"},"PeriodicalIF":6.4000,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12009284/pdf/","citationCount":"0","resultStr":"{\"title\":\"Allogeneic RPE cell suspension manufactured at scale demonstrating preclinical safety and efficacy led to IND approval.\",\"authors\":\"Lalitha Soundararajan, Harshini Surendran, Niharika Patlolla, Rajani Battu, Jonathan Stoddard, Sebastian Arrizabalaga, Zengping Liu, Gopal Lingam, Xinyi Su, Renee C Ryals, Rajarshi Pal\",\"doi\":\"10.1038/s41536-025-00407-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Cell replacement therapy is a promising therapeutic option for dry age-related macular degeneration (AMD). In this study, we outline our design for scalable manufacture with appropriate quality gates and present in vivo data for establishing preclinical safety and efficacy of an induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) product, thus laying the foundation for Phase 1/2a trial approval in India (ClinicalTrials.gov ID: NCT06394232; date of registration: 23<sup>rd</sup> September 2024). Escalating doses of RPE cell suspension in immunocompromised animals demonstrated absence of tumor formation up to 9 months post-injection. Good Laboratory Practices (GLP) toxicology and tolerability studies in rabbits and non-human primates (NHP) respectively showed no major adverse events. RPE transplanted into immune suppressed RCS rats showed integration, neuroprotection and rescue of visual function. In addition, we provide a detailed description of the modifications in GMP manufacturing protocol to create a final product with a unique composition and Chemistry, Manufacturing and Controls (CMC) studies performed during product development.</p>\",\"PeriodicalId\":54236,\"journal\":{\"name\":\"npj Regenerative Medicine\",\"volume\":\"10 1\",\"pages\":\"19\"},\"PeriodicalIF\":6.4000,\"publicationDate\":\"2025-04-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12009284/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"npj Regenerative Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41536-025-00407-0\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL & TISSUE ENGINEERING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"npj Regenerative Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41536-025-00407-0","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
Allogeneic RPE cell suspension manufactured at scale demonstrating preclinical safety and efficacy led to IND approval.
Cell replacement therapy is a promising therapeutic option for dry age-related macular degeneration (AMD). In this study, we outline our design for scalable manufacture with appropriate quality gates and present in vivo data for establishing preclinical safety and efficacy of an induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) product, thus laying the foundation for Phase 1/2a trial approval in India (ClinicalTrials.gov ID: NCT06394232; date of registration: 23rd September 2024). Escalating doses of RPE cell suspension in immunocompromised animals demonstrated absence of tumor formation up to 9 months post-injection. Good Laboratory Practices (GLP) toxicology and tolerability studies in rabbits and non-human primates (NHP) respectively showed no major adverse events. RPE transplanted into immune suppressed RCS rats showed integration, neuroprotection and rescue of visual function. In addition, we provide a detailed description of the modifications in GMP manufacturing protocol to create a final product with a unique composition and Chemistry, Manufacturing and Controls (CMC) studies performed during product development.
期刊介绍：
Regenerative Medicine, an innovative online-only journal, aims to advance research in the field of repairing and regenerating damaged tissues and organs within the human body. As a part of the prestigious Nature Partner Journals series and in partnership with ARMI, this high-quality, open access journal serves as a platform for scientists to explore effective therapies that harness the body's natural regenerative capabilities. With a focus on understanding the fundamental mechanisms of tissue damage and regeneration, npj Regenerative Medicine actively encourages studies that bridge the gap between basic research and clinical tissue repair strategies.
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