Cultivated autologous limbal epithelial cell (CALEC) transplantation for limbal tem cell deficiency: a phase I/II clinical trial of the first xenobiotic-free, serum-free, antibiotic-free manufacturing protocol developed in the US.

We developed a two-stage manufacturing process utilizing cultivated autologous limbal epithelial cells (CALEC), the first xenobiotic-free, serum-free, antibiotic-free protocol developed in the United States, to treat blindness caused by unilateral limbal stem cell deficiency (LSCD) and conducted a single-center, single-arm, phase I/II clinical trial. Primary outcomes were feasibility (meeting release criteria) and safety (ocular infection, corneal perforation, or graft detachment). Participant eligibility included male or female participants age 18 to <90 years old and ability to provide written informed consent with LSCD. Funding was provided by the National Eye Institute of the National Institutes of Health. CALEC grafts met release criteria in 14 (93%) of 15 participants at conclusion of trial. After first stage manufacturing, intracellular adenosine triphosphate levels correlated with colony forming efficiency (r = 0.65, 95% CI [0.04, 0.89]). One bacterial infection occurred unrelated to treatment, with no other primary safety events. The secondary outcome was to investigate efficacy based on improvement in corneal epithelial surface integrity (complete success) or improvement in corneal vascularization and/or participant symptomatology as measured by OSDI and SANDI (partial success). 86%, 93%, and 92% of grafts resulted in complete or partial success at 3, 12, and 18 months, respectively. Our results provide strong support that CALEC transplantation is safe and feasible and further studies are needed to evaluate therapeutic efficacy. Clinicaltrials.gov registration: NCT02592330.