Patient Stem Cells Repair Cornea Damage in Phase I Trial

A team led by researchers from Mass Eye and Ear, a member of Mass General Brigham, reports the results of a phase I trial of a revolutionary stem cell treatment called cultivated autologous limbal epithelial cell transplantation (CALEC), which was found to be safe and well-tolerated over the short term in four patients with significant chemical burns in one eye.

According to a study published August 18 in Science Advances, the patients who were followed for 12 months experienced restored cornea surfaces—two were able to undergo a corneal transplant and two reported significant improvements in vision without additional treatment.

While the phase I study was designed to determine preliminary safety and feasibility before advancing to a second phase of the trial, the researchers consider the early findings promising.

"Our early results suggest that CALEC might offer hope to patients who had been left with untreatable vision loss and pain associated with major cornea injuries," said principal investigator and lead study author Ula Jurkunas, MD, associate director of the Cornea Service at Mass Eye and Ear and an associate professor of ophthalmology at Harvard Medical School.

"Cornea specialists have been hindered by a lack of treatment options with a high safety profile to help our patients with chemical burns and injuries that render them unable to get an artificial cornea transplant. We are hopeful with further study, CALEC can one day fill this crucially needed treatment gap."

In CALEC, stem cells from a patient's healthy eye are removed via a small biopsy and then expanded and grown on a graft via an innovative manufacturing process at the Connell and O'Reilly Families Cell Manipulation Core Facility at Dana-Farber Cancer Institute. After two to three weeks, the CALEC graft is sent back to Mass Eye and Ear and transplanted into the eye with corneal damage.

The CALEC project is a collaboration between Jurkunas and colleagues in the Cornea Service at Mass Eye and Ear, researchers at Dana-Farber Cancer Institute, led by Jerome Ritz, MD, Boston Children's Hospital, led by Myriam Armant, Ph.D., and the JAEB Center for Health Research.

Using Patients’ Own Stem Cells to Overcome Treatment Limitations

People who experience chemical burns and other eye injuries may develop limbal stem cell deficiency, an irreversible loss of cells on the tissue surrounding the cornea. These patients experience permanent vision loss, pain and discomfort in the affected eye. Without limbal cells and a healthy eye surface, patients are unable to undergo artificial cornea transplants, the current standard of vision rehabilitation.

Existing treatment strategies have limitations and associated risks the CALEC procedure aims to address through its unique approach of using a small amount of a patient's own stem cells that can then be grown and expanded to create a sheet of cells that serves as a surface for normal tissue to grow back.

According to the authors, despite landmark studies describing an autologous stem cell approach over the past 25 years and similar methods being utilized in Europe, no U.S. research team had successfully developed a manufacturing process and quality control tests that met U.S. Food and Drug Administration (FDA) requirements or showed any clinical benefit.

"It was challenging to develop a process for creating limbal stem cell grafts that would meet the FDA's strict regulatory requirements for tissue engineering," said Ritz, executive director of the Connell and O'Reilly Families Cell Manipulation Core Facility at Dana-Farber and professor of medicine at Harvard Medical School. "Having developed and implemented this process, it was very gratifying to see encouraging clinical outcomes in the first cohort of patients enrolled on this clinical trial."

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. The Institute's multidisciplinary approach sets it apart from others in the space, helping researchers to rapidly advance new therapies and pushing the technological and clinical boundaries of this new frontier.

For individuals who experience chemical burns and other eye injuries, limbal stem cell deficiency can develop, leading to irreversible cell loss around the cornea. This condition results in permanent vision loss, pain, and discomfort in the affected eye. As current treatment strategies have limitations and associated risks, CALEC aims to address these issues by utilizing a small number of patients’ own stem cells. These cells are expanded to create a sheet that serves as a foundation for normal tissue to regenerate.

The authors noted that despite prior studies on autologous stem cell approaches and similar methods used in Europe over the past 25 years, no U.S. research team had successfully developed a manufacturing process and quality control tests meeting both U.S. Food and Drug Administration (FDA) standards and demonstrating clinical benefits. According to Ritz, the executive director of the Connell and O'Reilly Families Cell Manipulation Core Facility at Dana-Farber and a professor of medicine at Harvard Medical School, the process of creating limbal stem cell grafts meeting FDA requirements was challenging but ultimately rewarding.

This study underscores the potential of cell therapy in addressing previously incurable conditions. Mass General Brigham's Gene and Cell Therapy Institute plays a crucial role in translating researchers' scientific discoveries into initial clinical trials and ultimately transformative treatments for patients. Through a multidisciplinary approach, the institute accelerates the development of new therapies and pushes the boundaries of this emerging field.

Case Studies Show Promise as Clinical Trial Progresses

During the phase I study, five patients with chemical burns to one eye were enrolled and biopsied. Among them, four underwent CALEC treatment, while the cells from the fifth patient were found to have insufficient expansion ability after a series of quality control tests. The progress of the CALEC-treated patients was monitored over a 12-month period.

The initial patient, a 46-year-old male, witnessed the resolution of his eye surface defect, setting the stage for him to undergo an artificial cornea transplant to restore his vision. Likewise, the second patient, a 31-year-old male, experienced a comprehensive alleviation of symptoms, leading to an improvement in vision from 20/40 to 20/30.

Similarly, the third patient, a 36-year-old male, saw the resolution of his corneal defect and a vision enhancement from merely perceiving broad movements like waving to a 20/30 vision level.

In contrast, the fourth patient, a 52-year-old male, initially faced challenges with a biopsy that did not yield a viable stem cell graft. After undergoing another CALEC attempt three years later, he successfully underwent a transplant, leading to an improvement in his vision from hand motion to the ability to count fingers. Subsequently, he received an artificial cornea.

The researchers are currently in the process of finalizing the next phase of the clinical trial, involving 15 CALEC patients who will be monitored for 18 months. This extended monitoring aims to offer a more comprehensive understanding of the overall effectiveness of the procedure. The researchers aspire for CALEC to eventually emerge as a viable treatment option for patients who, due to the severity of their injuries, were previously left with enduring long-term deficits when conventional treatment options were not feasible.

Reference

Ula Jurkunas, Cultivated autologous limbal epithelial cell (CALEC) transplantation: development of manufacturing process and clinical evaluation of feasibility and safety, Science Advances (2023). DOI: 10.1126/sciadv.adg6470. www.science.org/doi/10.1126/sciadv.adg6470

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