Stem Cell Therapy CALEC Restores Corneal Damage in Trial Led by Massachusetts Eye and Ear Investigators

This article originally appeared on our sister site, Ophthalmology Times Europe®.

A therapy known as cultivated autologous limbal epithelial cells (CALEC) transplantation showed over 90% partial and complete success rates in repairing the corneal surfaces that had corneal damage believed to be irreversible, according to data from a phase 1/2 clinical trial (Clinicaltrials.gov registration: NCT02592330) that was published in Nature Communications.¹ The study is led by investigators at the Massachusetts Eye and Ear in Boston, including Ula Jurkunas, MD, PhD, who is associate director of the Cornea Service at the Mass Eye and Ear and professor of Ophthalmology at Harvard Medical School, Boston.

According to the investigators, the clarity of the cornea is dependent upon the regenerative capacity of the limbal epithelial stem cells.² These cells are found in the corneal limbus and continuously provide specialised corneal epithelium while serving as a barrier between the conjunctiva and cornea.³ Conjunctivalisation of the corneal surface and other signs of diminished integrity of the corneal epithelium, such as neovascularisation, inflammation, scarring and opacity, which lead to decreased vision and debilitating symptoms such as pain, photophobia, and tearing, characterize limbal stem cell deficiency (LSCD).⁴ Re-establishing a healthy ocular surface and adjacent limbal niche to support limbal epithelial stem cells is the objective of treatment intended to manage LSCD.^5,6

CALEC procedure

According to the investigators, CALEC, which was developed at the Mass Eye and Ear, constitutes the “first xenobiotic-free, serum-free, antibiotic-free protocol developed in the United States."

A 2-stage manufacturing process developed by Jurkunas and colleagues is used for CALECs intended to treat blindness caused by unilateral LSCD. In the study, the CALECs, which were derived from healthy eyes via biopsy, were expanded into a cellular tissue graft. This graft was surgically transplanted into eyes with damaged corneas.

According to Jurkanas, findings from an experimental stem cell treatment previously conducted on 4 eyes suggested that the approach was feasible and safe. As such, the new study was informed by these results.

The primary end points were the feasibility as assessed by meeting of release criteria and safety as assessed by the nonpresence of ocular infection, corneal perforation, or graft detachment. The study's secondary end point was efficacy as assessed by improvement in the corneal epithelial surface integrity (complete success) or improvement in corneal vascularisation and/or participant symptomatology as measured by the Ocular Surface Disease Index and the Symptom Assessment in Dry Eye (partial success) questionnaires.

CALEC results

According to a press release from Massachusetts Eye and Ear, the results were as follows:

1. CALEC completely restored the cornea in 50% of participants at their 3-month visit and that rate of complete success increased to 79% and 77% at their 12- and 18-month visits, respectively.
2. With 2 participants meeting the definition of partial success at 12 and 18 months, the overall success of CALEC was 93% and 92% at 12 and 18 months. Three participants received a second CALEC transplant, one of whom achieved complete success by the last study visit. An additional analysis of CALEC’s impact on vision showed varying levels of improvement of visual acuity in all 14 patients who underwent the procedure.
3. CALEC displayed a high safety profile, with no serious events occurring in either the donor or recipient eyes. A bacterial infection occurred in 1 participant 8 months after the transplant due to chronic contact lens use. Other adverse events were minor and resolved quickly following the procedures.

In commenting on their findings, the authors said, “Our results provide strong support that CALEC transplantation is safe and feasible and further studies are needed to evaluate the therapeutic efficacy. The results of this trial will serve as a stepping-stone for establishing cellular therapy products as viable options for patients with LSCD.”

The goal is to move on to a phase 3 study.

CALEC is still an experimental procedure and is not offered at Mass Eye and Ear or any hospital in the US or elsewhere. Additional studies will be necessary before the treatment is submitted for federal approval. The study was funded entirely by the NIH, the first human stem cell therapy trial to be funded by the NEI. The CALEC patent is pending. Jurkunas and Reza Dana, a coauthor from the Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, have financial interests in OcuCell, Inc.

References

1. Jurkunas U, Kaufman AR, Yin J, et al. Cultivated autologous limbal epithelial cell (CALEC) transplantation for limbal stem cell deficiency: a phase I/II clinical trial of the first xenobiotic-free, serum-free, antibiotic-free manufacturing protocol developed in the US. Nat Comm. doi: 10.1038/s41467-025-56461-1
2. Tseng SC. Concept and application of limbal stem cells. Eye (Lond). 1989;3:141–157.
3. Townsend WM. The limbal palisades of Vogt. Trans Am Ophthalmol Soc. 1991;89:721–756.
4. Deng SX, Borderie V, Chan CC, et al. Global consensus on definition, classification, diagnosis, and staging of limbal stem cell deficiency. Cornea. 2019;38:364–375.
5. Deng SX, Kruse F, Gomes JAP, et al. Global consensus on the management of limbal stem cell deficiency. Cornea. 2020;39:1291–1302.
6. Masood F, Chang J-H, Akbar A, et al. Therapeutic strategies for restoring perturbed corneal epithelial homeostasis in limbal stem cell deficiency: current trends and future directions. Cells. 2022;11:3247. doi: 10.3390/cells11203247

Ula Jurkunas, MD, PhD | E: [email protected]

Dr Jurkunas is from the Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston. She has a financial interest in OcuCell, Inc.