Abstract
Purpose :
Purpose: The NT-501 implant contains NTC-201-6A cells that have been genetically engineered to express and secrete human CNTF. The cell line is encapsulated in a semi-permeable membrane that allows for the diffusion of therapeutic protein into the vitreous. The implant is surgically placed into the vitreous cavity of the eye via a 3mm pars planar sclerotomy and sutured to the sclera. As with all therapeutic proteins there is a potential to develop antibodies against the therapeutic. This study was performed to determine if any immunogenicity was observed compared to a naïve population.
Methods :
Methods: A risk analysis for antibodies development was performed. Furthermore, direct ELISA-based assays were developed to determine if antibodies to hCNTF or intracellular NTC-201-6A mDHFR protein were present. A multi-tiered analysis was performed consisting of a screening assay and a confirmatory assay performed on positive samples and finally a titer was determined on confirmed positive samples. Baseline, 1, 3 and 6 month samples were analyzed, which would cover the most likely time frame of antibody production.
Results :
Results: In a six-month study of patients receiving two implants (NTMT-02B [NCT#04729972]), 3.2% of the serum samples evaluated were positive for antibodies against the secreted product protein CNTF, or to a non-secreted intracellular protein DHFR. In all cases, the antibodies were present prior to surgical placement of the implant, and the observed titer was low. Antibody positive samples did not neutralize the activity of CNTF in a cell-based bioassay. No subject experienced a treatment related increase in immunogenicity to NT-501 or intracellular components throughout the duration of the study. A similar frequency (3.6%) of low titer antibody positive samples was observed in a naïve population.
Conclusions :
Conclusion: These data suggest that patients did not mount an immune response to NT-501, and that the presence of antibodies is not treatment related.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.