An expanded phase 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 I/II trial are published in Nature Communications.
The technique, developed by researchers at Dana-Farber Cancer Institute, Massachusetts Eye and Ear, and Boston Children’s Hospital, is called cultivated autologous limbal epithelial cells (CALEC).
The innovative procedure involves removing stem cells from a healthy eye with a biopsy. Under the direction of Jerome Ritz, MD, the manufacturing of the stem cell graft takes place at Dana-Farber’s Connell and O'Reilly Families Cell Manipulation Core Facility (CMCF). Limbal stem cells derived from the biopsy are grown and expanded in a two-stage process that takes two to three weeks. After stringent quality control testing, the cellular tissue graft is returned to MEEI where it is surgically transplanted 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.”
Jerome Ritz, MD
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.
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.
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 CMCF at Dana-Farber. Dr. Myriam Armant, director of the TransLab at Boston Children’s Hospital helped develop the manufacturing process and performed some of the release testing for these products.
“It was great to see teams with very different kinds of expertise, work together to develop and implement a new therapy that improved the lives of these patients,” said Ritz.
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 Jerome Ritz, MD, executive director of the Connell and O’Reilly Families Cell Manipulation Core Facility at Dana-Farber and professor of medicine at Harvard Medical School. “This will hopefully expand the use of this approach and make it possible to treat patients who have damage to both eyes.”
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 additional studies will be needed before the treatment is submitted for federal approval.
In the interim, future CALEC studies should include larger numbers of patients at multiple centers, with longer follow-ups and a randomized-control design.
Funding: This research is funded by National Eye Institute (NEI) of the National Institutes of Health (NIH) under Award Numbers UG1EY026508, UG1EY027726, and UG1EY027725. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
This press release was adapted from Massachusetts Eye and Ear, a member of the Mass General Brigham healthcare system.