CALEC Protocol
March 4, 2025 | Press Release
Novel Stem Cell Therapy Safely RepairsIrreversible Corneal Damage in Clinical Trial
Mass Eye and Ear-ledtrial of procedure that took stem cells from a healthy eye and transplantedthem into the damaged eye, safely restored corneal surfaces in 14 patients whowere followed for 18 months
An expanded phase clinical trial that tested agroundbreaking, experimental stem cell treatment for blinding cornea injuriesfound the treatment was feasible and safe in 14 patients who were treated andfollowed for 18 months, and there was a high proportion of complete or partialsuccess. The results of this phase I/II trial are published in NatureCommunications.
The treatment, called cultivated autologouslimbal epithelial cells (CALEC), was developed at Mass Eye and Ear, a member ofthe Mass General Brigham healthcare system. The innovative procedure consistsof removing stem cells from a healthy eye with a biopsy, expanding them into acellular tissue graft in a novel manufacturing process that takes two to threeweeks, and then surgically transplanting the graft into the eye with a damagedcornea.
“Our first trial in four patients showed thatCALEC was safe and the treatment was possible,” said principal investigator Ula Jurkunas, MD, associate director ofthe Cornea Service at Mass Eye and Ear and professor of Ophthalmology atHarvard Medical School. “Now we have this new data supporting that CALEC ismore than 90% effective at restoring the cornea’s surface, which makes ameaningful difference in individuals with cornea damage that was considereduntreatable.”
Researchers showed CALEC completelyrestored the cornea in 50% of participants at their 3-month visit and that rateof complete success increased to 79% and 77% at their 12- and 18-month visits,respectively.
With two participants meeting the definition ofpartial success at 12 and 18 months, the overall success of CALEC was 93% and92% at 12 and 18 months. Three participants received a second CALECtransplant, one of whom reached complete success by the study end visit. Anadditional analysis of CALEC’s impact on vision showed varying levels ofimprovement of visual acuity in all 14 CALEC patients.
CALEC displayed a high safety profile, with noserious events occurring in either the donor or recipient eyes. One adverseevent, a bacterial infection, occurred in one participant, eight months afterthe transplant due to chronic contact lens use. Other adverse events were minorand resolved quickly following the procedures.
CALEC remains an experimental procedure and iscurrently not offered at Mass Eye and Ear or any U.S. hospital, and additionalstudies will be needed before the treatment is submitted for federalapproval.
The CALEC trial is the first human study of astem cell therapy to be funded by the National Eye Institute (NEI), a part ofthe National Institutes of Health (NIH) and was the first stem cell therapy inthe 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 CancerInstitute’s Connell and O'ReillyFamilies Cell Manipulation Core Facility, where the manufacturing of the stem cellgraft takes place; and Myriam Armant, PhD, of Boston Children’sHospital; and the JAEB Center for HealthResearch.
The cornea is the clear, outermost layer of theeye. It’s outer border, the limbus, contains a large volume of healthy stemcells called limbal epithelial cells, which maintain the eye’s smooth surface.When a person suffers a cornea injury, such as a chemical burn, infection orother trauma, it can deplete the limbal epithelial cells, which can neverregenerate. The resulting limbal stem cell deficiency renders the eye with apermanently damaged surface where it can’t undergo a corneal transplant, the currentstandard of care for vision rehabilitation. People with these injuries oftenexperience persistent pain and visual difficulties.
This treatment gap led Jurkunas as a juniorscientist to explore methods of regenerating limbal epithelial cells. Nearlytwo decades later, following preclinical studies and collaborations withresearchers at Dana-Farber and Boston Children’s, it was possible toconsistently manufacture CALEC grafts that met stringent quality criterianeeded for human transplantation. The clinical trial was approved by the U.S.Food and Drug Administration (FDA) and Mass General Brigham InstitutionalReview Board (IRB) and the first patient was treated in 2018 at Mass Eye andEar. Successful completion of the trial was accomplished through closecoordination between Jurkunas’ surgical team and the cell manufacturingfacility 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 Dr. 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.”
Authorship: In addition to Jurkunas, Ritz and Armant, co-authors of the study include Aaron R. Kaufman (MEE), Jia Yin (MEE), Allison Ayala (Jaeb), Maureen Maguire (Jaeb), Lassana Samarakoon (Jaeb), Lynette K. Johns (MEE), Mohit Parekh (MEE), Sanming Li (MEE), Alex Gauthier (MEE), Helene Negre (DFCI), Kit L. Shaw (DFCI), Diego E. Hernandez Rodriguez (DFCI), Heather Daley (DFCI), and Reza Dana (MEE).
Disclosures: CALEC is patent pending. Jurkunas and Dana have financial interest in OcuCell, Inc., a company developing living ophthalmic cell-based therapies for treating eye disease. Armant serves on the scientific advisory board for OcuCell, Inc. Ritz receives research funding from Kite/Gilead, Novartis and Oncternal and serves on Scientific Advisory Boards for Astraveus, Garuda Therapeutics, Smart Immune, Tolerance Bio, and TriArm Therapeutics. The remaining authors declare no competing interests.
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.