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

Abstract

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

Acknowledgments

This work was supported by Janssen Research & Development, LLC. TM, an employee of Janssen, and RS, SF, and GPL, who have received research funding from Janssen for this study, were involved in the development of the study design; collection, analysis, and interpretation of data; writing of the report; and in the decision to submit the article for publication. The authors thank Darin J. Messina, PhD, for contributions in performing the ERM analyses. Editorial support for the writing of this case report was provided by Megan Knagge, PhD, of MedErgy, and was funded by Janssen Research & Development, LLC. The authors retained full editorial control over the content of the manuscript. All authors approved the final article.

Disclosure

TM is an employee of Janssen. RS, SF, and GPL received research funding from Janssen for this study. The authors report no other conflicts of interest in this work.