A pioneering clinical trial has demonstrated remarkable success in treating limbal stem cell deficiency (LSCD) using a novel cell therapy approach. The study, conducted at Massachusetts Eye and Ear, evaluated the safety and efficacy of Cultivated Autologous Limbal Epithelial Cell (CALEC) transplantation in patients with unilateral LSCD.
Clinical Trial Results and Safety Profile
The trial enrolled 15 participants between August 2016 and September 2021, with 14 receiving CALEC transplants. The manufacturing process achieved a 93% success rate, producing viable constructs that met rigorous FDA standards. Notably, the therapy demonstrated an exceptional safety profile, with only one primary safety event reported - a bacterial infection attributed to contact lens use rather than the treatment itself.
The manufacturing protocol utilized a standardized, two-stage process without animal components or antibiotics, distinguishing it from similar products available in other countries. Cell expansion provided sufficient material for quality control assays and two CALEC constructs per patient, with one serving as a backup graft.
Remarkable Efficacy Outcomes
The therapy showed impressive efficacy metrics:
- 86% complete or partial success at 3 months
- 93% complete or partial success at 12 months
- 92% complete or partial success at 18 months
Complete success was defined by improved corneal surface integrity, while partial success indicated improvements in corneal vascularization or patient symptoms. All participants achieved complete success during at least one visit, with nine maintaining this status throughout subsequent follow-ups.
Manufacturing and Biomarker Analysis
The manufacturing process consistently produced epithelial cells expressing high levels (~98%) of epithelial markers and low levels of hematopoietic/endothelial markers. Colony forming efficiency (CFE) showed correlation with manufacturing timeline and intracellular adenosine triphosphate (iATP) levels, suggesting potential quality indicators for future production.
Clinical Implications and Future Directions
CALEC's success rate of 77% at 18 months for corneal surface integrity compares favorably with existing treatments. The therapy demonstrated particular effectiveness in both mild and severe LSCD cases, with improvements in corneal surface integrity, neovascularization, and patient symptoms.
The study revealed that recipient microenvironment and macro-environment factors significantly influence treatment success, suggesting the importance of optimizing the ocular surface before grafting. While the trial had limitations, including gender distribution skew and lack of a randomized control arm, the results strongly support further investigation through larger, multi-center trials.
