Novel Stem Cell Therapy Repairs Irreversible Corneal Damage in Clinical Trial

An expanded clinical trial that tested a groundbreaking, experimental stem cell treatment for blinding cornea injuries found the treatment was feasible and safe in 14 patients who were treated and followed for 18 months, and there was a high proportion of complete or partial success. The results of this new phase 1/2 trial are published in Nature Communications.

The treatment, called cultivated autologous limbal epithelial cells (CALEC), was developed at Mass Eye and Ear, a member of the Mass General Brigham healthcare system. The innovative procedure consists of removing stem cells from a healthy eye with a biopsy, expanding them into a cellular tissue graft in a novel manufacturing process that takes two to three weeks, and then surgically transplanting the graft into the eye with a damaged cornea.

“Our first trial in four patients showed that CALEC was safe and the treatment was possible,” said principal investigator Ula Jurkunas, MD, associate director of the Cornea Service at Mass Eye and Ear and professor of Ophthalmology at Harvard Medical School. “Now we have this new data supporting that CALEC is more than 90% effective at restoring the cornea’s surface, which makes a meaningful difference in individuals with cornea damage that was considered untreatable.”

Researchers showed 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.  

With two 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 reached complete success by the study end visit. An additional analysis of CALEC’s impact on vision showed varying levels of improvement of visual acuity in all 14 CALEC patients.

CALEC displayed a high safety profile, with no serious events occurring in either the donor or recipient eyes. One adverse event, a bacterial infection, occurred in one participant, eight months after the transplant due to chronic contact lens use. Other adverse events were minor and resolved quickly following the procedures.

CALEC remains an experimental procedure and is currently not offered at Mass Eye and Ear or any U.S. hospital, and additional studies will be needed before the treatment is submitted for federal approval.

The CALEC trial is the first human study of a stem cell therapy to be funded by the National Eye Institute (NEI), a part of the National Institutes of Health (NIH) and was the first stem cell therapy in the eye in the U.S. Other research collaborators include Jia Yin, MD, PhD, and Reza Dana, MD, at Mass Eye and Ear, Jerome Ritz, MD, of Dana-Farber Cancer Institute’s Connell and O'Reilly Families Cell Manipulation Core Facility, where the manufacturing of the stem cell graft takes place; and Myriam Armant, PhD, of Boston Children’s Hospital; and the JAEB Center for Health Research.

The cornea is the clear, outermost layer of the eye. It’s outer border, the limbus, contains a large volume of healthy stem cells called limbal epithelial cells, which maintain the eye’s smooth surface. When a person suffers a cornea injury, such as a chemical burn, infection or other trauma, it can deplete the limbal epithelial cells, which can never regenerate. The resulting limbal stem cell deficiency renders the eye with a permanently damaged surface where it can’t undergo a corneal transplant, the current standard of care for vision rehabilitation. People with these injuries often experience persistent pain and visual difficulties.

This need led Jurkunas as a junior scientist and Dana, director of the Cornea Service at Mass Eye and Ear, to explore a new approach for regenerating limbal epithelial cells. Nearly two decades later, following preclinical studies and collaborations with researchers at Dana-Farber and Boston Children’s, it was possible to consistently manufacture CALEC grafts that met stringent quality criteria needed for human transplantation. The clinical trial was approved by the U.S. Food and Drug Administration (FDA) and Mass General Brigham Institutional Review Board (IRB) and the first patient was treated in 2018 at Mass Eye and Ear. Successful completion of the trial was accomplished through close coordination between Jurkunas’ surgical team and the cell manufacturing facility at Dana-Farber.

Studies like this show the promise of cell therapy for treating incurable conditions. Mass General Brigham’s Gene and Cell Therapy Institute is helping to translate scientific discoveries made by researchers into first-in-human clinical trials and, ultimately, life-changing treatments for patients.

As an autologous therapy, one limitation of this approach is that it is necessary for the patient to have only one involved eye so a biopsy can be performed to get starting material from the unaffected normal eye.

“Our future hope is to set up an allogeneic manufacturing process starting with limbal stem cells from a normal cadaveric donor eye,” said Ritz “This will hopefully expand the use of this approach and make it possible to treat patients who have damage to both eyes.”

In the interim, future CALEC studies should include larger numbers of patients at multiple centers, with longer follow-ups and a randomized-control design.

“We feel this research warrants additional trials that can help lead towards FDA approval,” said Jurkunas. “While we are proud to have been able to bring a new treatment from the lab bench to clinical trials, our guiding objective was and always will be for patients around the country to have access to this effective treatment.”