Palucorcel (CNTO 2476) is currently being evaluated as a novel cell-based therapy for the treatment of GA secondary to AMD. Palucorcel is composed of human umbilical cord tissue–derived cells (hUTC),
17 and the nature and characterization of these cells has been reported previously.
18 The cells are supplied in a proprietary cryopreserved formulation that is thawed shortly before use according to the manufacturer's instructions. Subretinal administration of palucorcel was associated with preservation of visual function in a rat model of retinal degeneration.
17 Subsequent in vitro studies showed that palucorcel was capable of rescuing RPE phagocytic dysfunction, promoting excitatory synaptic connectivity, enhancing neuronal survival, and enhancing neurite outgrowth via paracrine signaling pathways.
19,20 A recent phase 1/2a study evaluated the administration of palucorcel in 35 adults, 50 years of age and older, with bilateral GA secondary to AMD. A microcatheter delivery system (iTrack 275; iScience, Inc., Menlo Park, CA, USA) was used in conjunction with an ab externo surgical approach to access the subretinal space.
18 Palucorcel was well tolerated when delivered without retinal perforation. There was no clinical evidence of an immune response, cell rejection, or tumor formation.
18 The low humoral immunogenicity of palucorcel observed in the phase 1/2a study was supported by previous preclinical studies showing that a single injection of pig umbilical tissue–derived cells (pUTC) in minipigs was not associated with a detectable immune response.
21,22 Although palucorcel was well tolerated in the phase 1/2a study, the ab externo surgical approach required to access the subretinal space with the microcatheter delivery system was associated with a high rate of retinal perforations (13/35 operated subjects) and retinal detachments (6/35 operated subjects).
18 In another phase 1 study in subjects with retinitis pigmentosa, inadvertent seeding into the vitreous cavity, while injecting palucorcel into the subretinal space via a transvitreal approach, was associated with retinal detachment, as well as the formation of epiretinal membranes.
23 The occurrence of retinal detachments and perforations in both early studies highlighted the need to develop a safer targeted surgical technique to deliver palucorcel into the subretinal space.