Epiretinal membrane in a subject after transvitreal delivery of palucorcel (CNTO 2476)

Rand Spencer,1 Steven Fisher,2 Geoffrey P Lewis,3 Terri Malone4 1Texas Retina Associates, Dallas, TX, USA; 2Molecular, Cellular, and Developmental Biology, 3Center for the Study of Macular Degeneration, Neuroscience Research Institute, University of California, Santa Barbara, CA, 4Cell Therapy, Jan...

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Autores principales:	Spencer R, Fisher S, Lewis GP, Malone T
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	cell therapy epiretinal membrane retinitis pigmentosa Ophthalmology RE1-994
Acceso en línea:	https://doaj.org/article/8d1851f446a24821aaf70c6d46d833b6
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spelling	oai:doaj.org-article:8d1851f446a24821aaf70c6d46d833b62021-12-02T07:07:27ZEpiretinal membrane in a subject after transvitreal delivery of palucorcel (CNTO 2476)1177-5483https://doaj.org/article/8d1851f446a24821aaf70c6d46d833b62017-10-01T00:00:00Zhttps://www.dovepress.com/epiretinal-membrane-in-a-subject-after-transvitreal-delivery-of-paluco-peer-reviewed-article-OPTHhttps://doaj.org/toc/1177-5483Rand Spencer,1 Steven Fisher,2 Geoffrey P Lewis,3 Terri Malone4 1Texas Retina Associates, Dallas, TX, USA; 2Molecular, Cellular, and Developmental Biology, 3Center for the Study of Macular Degeneration, Neuroscience Research Institute, University of California, Santa Barbara, CA, 4Cell Therapy, Janssen Research & Development, LLC, Spring House, PA, USA Background: A 70-year-old woman with retinitis pigmentosa experienced an epiretinal membrane (ERM) formation and a tractional retinal detachment (RD) following subretinal administration of palucorcel (CNTO 2476), a novel human umbilical tissue-derived cell-based therapy, as part of a Phase I study. The clinical course and results of a histologic examination of the ERM, which was peeled during surgery to repair the RD, are described here.Methods: In this open-label, first-in-human, Phase I study (NCT00458575), two of seven subjects developed RD, with an ERM formation reported in a woman receiving a targeted dose of 3.0×105 palucorcel administered via a transvitreal route. A sample of the ERM was retained for analysis following the ERM peeling procedure. Clinical outcomes and ERM histology, based on immunocytochemistry analyses and fluorescence in situ hybridization (FISH) staining, were evaluated.Results: We first noted the RD and formation of the ERM at 26 days after palucorcel administration. The ERM was cellular and contained multiple cell types, including Müller glial cells, immune cells, neurites, retinal pigment epithelial cells, and palucorcel. The majority of cells were not actively dividing. FISH staining showed a subset of Y chromosome-positive cells in the ERM from this woman, supporting the presence of palucorcel (derived from umbilical cord tissue of male neonate). Palucorcel did not differentiate into Müller glia, immune cells, neurites, or retinal pigment epithelial cells.Discussion: The development of an ERM containing both subject (self) cells and palucorcel suggests that palucorcel egress in the vitreal cavity after retinotomy may contribute to ERM formation and RD and that an alternative delivery method will be required before further studies are conducted. Subsequent clinical research using alternative subretinal delivery methods for palucorcel in other indications suggests that membrane development does not occur when palucorcel is delivered without retinal perforation. Keywords: cell therapy, epiretinal membrane, retinitis pigmentosaSpencer RFisher SLewis GPMalone TDove Medical Pressarticlecell therapyepiretinal membraneretinitis pigmentosaOphthalmologyRE1-994ENClinical Ophthalmology, Vol Volume 11, Pp 1797-1803 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	cell therapy epiretinal membrane retinitis pigmentosa Ophthalmology RE1-994
spellingShingle	cell therapy epiretinal membrane retinitis pigmentosa Ophthalmology RE1-994 Spencer R Fisher S Lewis GP Malone T Epiretinal membrane in a subject after transvitreal delivery of palucorcel (CNTO 2476)
description	Rand Spencer,1 Steven Fisher,2 Geoffrey P Lewis,3 Terri Malone4 1Texas Retina Associates, Dallas, TX, USA; 2Molecular, Cellular, and Developmental Biology, 3Center for the Study of Macular Degeneration, Neuroscience Research Institute, University of California, Santa Barbara, CA, 4Cell Therapy, Janssen Research & Development, LLC, Spring House, PA, USA Background: A 70-year-old woman with retinitis pigmentosa experienced an epiretinal membrane (ERM) formation and a tractional retinal detachment (RD) following subretinal administration of palucorcel (CNTO 2476), a novel human umbilical tissue-derived cell-based therapy, as part of a Phase I study. The clinical course and results of a histologic examination of the ERM, which was peeled during surgery to repair the RD, are described here.Methods: In this open-label, first-in-human, Phase I study (NCT00458575), two of seven subjects developed RD, with an ERM formation reported in a woman receiving a targeted dose of 3.0×105 palucorcel administered via a transvitreal route. A sample of the ERM was retained for analysis following the ERM peeling procedure. Clinical outcomes and ERM histology, based on immunocytochemistry analyses and fluorescence in situ hybridization (FISH) staining, were evaluated.Results: We first noted the RD and formation of the ERM at 26 days after palucorcel administration. The ERM was cellular and contained multiple cell types, including Müller glial cells, immune cells, neurites, retinal pigment epithelial cells, and palucorcel. The majority of cells were not actively dividing. FISH staining showed a subset of Y chromosome-positive cells in the ERM from this woman, supporting the presence of palucorcel (derived from umbilical cord tissue of male neonate). Palucorcel did not differentiate into Müller glia, immune cells, neurites, or retinal pigment epithelial cells.Discussion: The development of an ERM containing both subject (self) cells and palucorcel suggests that palucorcel egress in the vitreal cavity after retinotomy may contribute to ERM formation and RD and that an alternative delivery method will be required before further studies are conducted. Subsequent clinical research using alternative subretinal delivery methods for palucorcel in other indications suggests that membrane development does not occur when palucorcel is delivered without retinal perforation. Keywords: cell therapy, epiretinal membrane, retinitis pigmentosa
format	article
author	Spencer R Fisher S Lewis GP Malone T
author_facet	Spencer R Fisher S Lewis GP Malone T
author_sort	Spencer R
title	Epiretinal membrane in a subject after transvitreal delivery of palucorcel (CNTO 2476)
title_short	Epiretinal membrane in a subject after transvitreal delivery of palucorcel (CNTO 2476)
title_full	Epiretinal membrane in a subject after transvitreal delivery of palucorcel (CNTO 2476)
title_fullStr	Epiretinal membrane in a subject after transvitreal delivery of palucorcel (CNTO 2476)
title_full_unstemmed	Epiretinal membrane in a subject after transvitreal delivery of palucorcel (CNTO 2476)
title_sort	epiretinal membrane in a subject after transvitreal delivery of palucorcel (cnto 2476)
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/8d1851f446a24821aaf70c6d46d833b6
work_keys_str_mv	AT spencerr epiretinalmembraneinasubjectaftertransvitrealdeliveryofpalucorcelcnto2476 AT fishers epiretinalmembraneinasubjectaftertransvitrealdeliveryofpalucorcelcnto2476 AT lewisgp epiretinalmembraneinasubjectaftertransvitrealdeliveryofpalucorcelcnto2476 AT malonet epiretinalmembraneinasubjectaftertransvitrealdeliveryofpalucorcelcnto2476
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Epiretinal membrane in a subject after transvitreal delivery of palucorcel (CNTO 2476)

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