Results from a stem cell therapy clinical trial published in Science Advances demonstrated positive data supporting the use of cultivated autologous limbal epithelial cell (CALEC) transplantation to potentially regenerate the corneal environment.
Give me some background first.
Limbal stem cell deficiency (LSCD) can lead to vision loss, pain, and an impaired quality of life (QoL).
While standard corneal transplantation can rehabilitate the central cornea depending on severity, it’s unable to treat LSCD directly.
Therapeutic strategies for replacing the limbal epithelium (such as limbal autografts) often come with a high risk for rejection and require long-term systemic immunosuppression.
As a possible solution to avoid these risks, previous research methods have used expanded LSC ex vivo leveraging a technique called cultivated limbal epithelial transplantation (CLET) —not currently available in the United States.
How does this relate to this new research?
Researchers from Massachusetts Eye and Ear Infirmary (MEE) developed the CALEC manufacturing process to address shortcomings associated with the CLET process, such as a high risk for:
- Viral contaminants
- Inflammatory response against murine antigens (antibodies)
Tell me about CALEC.
The technique is designed without the risk of cell rejection by performing a small biopsy to harvest cells from the patient’s non-diseased eye to then expand and grow on a graft via a manufacturing process developed at the Connell and O'Reilly Families Cell Manipulation Core Facility at the Dana-Farber Cancer Institute in Boston, Massachusetts.
The resulting sheet of cells that are created serve as a substrate for normal tissue to grow back.
And how was it tested?
The researchers conducted an open-label, single-center phase 1 clinical trial (NCT02592330) assessing the CALEC technique applied to a cohort of four male patients with unilateral LSCD due to chemical burns.
Patients were then tracked for 12 months.
Findings?
At Month 12, all four patients experienced a restoration of their cornea surface, with two eligible for corneal transplantation and the other two reporting significant vision improvements (with no additional treatment).
To note, Patient 4’s initial biopsy was unsuccessful; CALEC was successfully performed 3 years later.
Give me specifics.
We’ll take it patient-by-patient:
- Patient 1
- Age 46
- Neovascularization reduction
- Epithelial defect resolution
- Eligible for corneal transplantation
- Patient 2
- Age 31
- Corneal staining improvement
- Best-corrected visual acuity (BCVA) improvement: 20/40 (baseline) to 20/30
- Patient 3
- Age 36
- Epithelial defect resolution
- BCVA improved from hand motion (baseline) to 20/30
- Patient 4
- Age 52
- BCVA improved from hand motion (baseline) to counting fingers.
- Eligible for corneal transplantation
Significance?
This trial is the first human study of a stem cell therapy to be funded by the National Eye Institute (NEI).
So what’s next?
The next phase of the trial is currently being finalized, with a planned 15 patients to undergo CALEC and be tracked for 18 months.
And the overall goal?
Per MEE, investigators hope for CALEC to become a treatment option for patients with significant corneal injuries who “previously had to endure long-term deficits when existing treatment options were not an option given the severity of their injuries.”