Dana-Farber Cancer Institute, Inc.

WEDNESDAY, March 5, 2025 -- Sight-robbing injuries to the cornea can be repaired using a groundbreaking experimental stem cell treatment, a new study shows. The cornea -- the clear outermost layer of the eye -- can become irreversibly damaged if injury or disease destroys its ability to regenerate new cells. In this new process, stem cells taken from a person’s healthy eye can be used to rebuild the cornea in their damaged eye, researchers reported March 4 in the journal Nature Communications . The process has proven feasible and safe in 14 patients who were treated and followed for 18 months, early clinical trial results show. The treatment is called cultivated autologous limbal epithelial cells, or CALEC. “Our first trial in four patients showed that CALEC was safe and the treatment was possible,” lead investigator Dr. Ula Jurkunas , associate director of the Cornea Service at Mass Eye and Ear in Boston, said in a news release. “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,” she said. The outer border of the cornea, the limbus, contains many healthy stem cells called limbal epithelial cells, researchers explained in background notes. These cells constantly rebuild the cornea, keeping it clear and smooth. When a person’s cornea is damaged, the injury can deplete the limbal epithelial cells. As a result, the surface of the eye develops permanent damage -- a condition called limbal stem cell deficiency. Worse, this damage can render the eye unfit for cornea replacement surgery, which replaces a damaged or diseased cornea with donor tissue, researchers said. CALEC involves removing stem cells from a healthy eye and then expanding them into a tissue graft using a new manufacturing process that takes two to three weeks, researchers explained. The graft is then surgically transplanted into the eye with a damaged cornea, restoring the cornea’s ability to regenerate. CALEC completely restored the cornea in half of study participants within three months, and that rate of success increased to around 80% after a year and a half, results show. The overall success rate of CALEC came in around 90% when considering those who achieved partial recovery, researchers said. The procedure also proved safe, with no serious adverse events occurring in either the donor or the damaged eye of the patients, researchers said. The procedure is still experimental, and further clinical trials will be needed before CALEC is submitted for federal approval, researchers said. “We feel this research warrants additional trials that can help lead towards [U.S. Food and Drug Administration] approval,” Jurkunas said. In the meantime, researchers hope to refine the procedure. For example, now a person must still have one healthy eye to serve as a stem cell donor to the damaged eye. Researchers eventually want to be able to perform the procedure using stem cells taken from the eyes of deceased donors. “This will hopefully expand the use of this approach and make it possible to treat patients who have damage to both eyes,” researcher Dr. Jerome Ritz , executive director of the Dana-Farber Cancer Institute's Cell Manipulation Core Facility, said in a news release. Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

Thirteen out of 14 people with eye damage experienced at least some improvements to their cornea after receiving a stem cell transplant in one eye in an early-stage study. The National Institutes of Health-funded Phase 1/2 trial was led by ophthalmologist Ula Jurkunas at Massachusetts Eye and Ear, and reported in Nature Communications. The patients in the study mostly had chemical or thermal burns to one eye, such as from a fireworks accident. There are stem cell treatments approved in other countries, such as Holoclar in the EU, to treat damage on the outer layer of the eye, or what’s known as limbal stem cell deficiency, when the eye can no longer properly regenerate its cornea usually after an injury. But the study authors said that the manufacturing procedures used in those treatments include methods that may not be FDA-compliant. “The FDA doesn’t like us to use antibiotics in the media, because that could cover up a potential infection,” said Dana-Farber Cancer Institute’s Jerome Ritz, who led the manufacturing of the stem cell therapies in the study. “The other procedures will grow the cells on ‘feeder cells.’ So, they actually have mouse cells that they grow first, and then they put the human cells on these mouse feeder cells. And the FDA doesn’t like that either,” Ritz added. “Then, the other thing is the FDA doesn’t like using serum,” he said, referring to a kind of supplement added to cell cultures that often come from animals. Jurkunas is a co-founder of the biotech OcuCell, which is working to develop cell therapies for eye conditions including limbal stem cell deficiency. Other biotechs such as Aurion Biotech (which is currently in a legal spat with its investor, the eye giant Alcon) are likewise developing cell therapies for conditions related to the cornea. The researchers previously reported early results from four people in this trial in 2023. Fifteen people were enrolled in the Mass Eye and Ear study and had a biopsy to obtain cells from their healthy eye. Of those patients, stem cell therapies were successfully manufactured for 14 patients. One patient needed two biopsies for their stem cell treatment to be successfully made. A key limitation of the study was that patients needed one eye that was healthy enough so the researchers could take a biopsy to make the stem cell therapy. Of the 14 participants who received transplants, 11 saw improvement in the outermost layer of their cornea and were considered “complete success” at one year. Two more were deemed a “partial success,” meaning they had improvements in their symptoms or fewer blood vessel formations around their eye, which can cause the cornea to become opaque. One patient saw no improvements. Jurkunas noted that vision wasn’t part of the key endpoint for the study, because the outer layer of the cornea is only one of the layers that is impacted when someone has a major eye injury. “There are many other layers in the cornea and the eye can get affected. And even though we restore the surface of the cornea, that does not mean that we fully restore all other layers, and the vision can still be impaired. However, when we restore epithelial cells, we can do other surgeries to improve the vision,” she said. “In some patients, it’s the first step towards next procedures like a full corneal transplant,” she added, noting that two patients went on to receive full corneal transplants after receiving the stem cell transplant. Jurkunas said although vision improvements were not the goal of the study, 71% saw vision improvements. In addition, there were no serious safety events in the donor or recipient’s eye. The researchers wrote in their paper that the next steps include developing an allogeneic stem cell therapy, where the cells would be from a donor and not from the patient’s other eye. That could enable treating patients with injuries to both eyes and at a greater scale. The clinical trial results are coming out at a time when NIH funding is coming under attack from the Trump administration. “I would point out that not only was the clinical trial funded — that was funded by the National Eye Institute — but also the pre-clinical development going back 10, 12 years, that was also funded by the NIH,” Ritz said. “We’ve been very fortunate to have federal support. We haven’t had commercial support for any of this. That’s all been done through funding from the NIH.” “The important part is that commercial partners probably wouldn’t necessarily find it appealing to fund these early-stage trials because they just don’t have as much evidence of the feasibility,” Jurkunas said. “So it was really critical for NIH to fund our trial in this early stage.”

FRIDAY, Feb. 21, 2025 -- For patients with previously untreated chronic lymphocytic leukemia (CLL), fixed-duration acalabrutinib-venetoclax with or without obinutuzumab significantly prolongs progression-free survival compared with chemoimmunotherapy, according to a study published online Feb. 5 in the New England Journal of Medicine . Jennifer R. Brown, M.D., from Dana-Farber Cancer Institute in Boston, and colleagues conducted a phase 3, open-label trial involving patients with CLL aged 18 years or older with an Eastern Cooperative Oncology Group performance-status score of 0 to 2, who did not have a 17p deletion or TP53 mutation. Patients were randomly assigned to receive acalabrutinib-venetoclax, acalabrutinib-venetoclax-obinutuzumab, or chemoimmunotherapy with the investigator's choice of fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab (291, 286, and 290 [143 and 147], respectively). The researchers found that at a median follow-up of 40.8 months, the estimated 36-month progression-free survival was 76.5, 83.1, and 66.5 percent with acalabrutinib-venetoclax, acalabrutinib-venetoclax-obinutuzumab, and chemoimmunotherapy, respectively (hazard ratio for disease progression or death, 0.65 [P = 0.004], for acalabrutinib-venetoclax versus chemoimmunotherapy; P < 0.001 for acalabrutinib-venetoclax-obinutuzumab versus chemoimmunotherapy). The estimated 36-month overall survival was 94.1, 87.7, and 85.9 percent with acalabrutinib-venetoclax, acalabrutinib-venetoclax-obinutuzumab, and chemoimmunotherapy, respectively. The most common adverse event of clinical interest of grade 3 or higher was neutropenia, which was reported in 32.3, 46.1, and 43.2 percent in the three groups, respectively. Ten, 25, and 21 patients died from COVID-19 in the three groups, respectively. "Continued follow-up will be essential to clarify which patients would be most suitable for acalabrutinib-venetoclax and which for acalabrutinib-venetoclax-obinutuzumab," the authors write. Several authors disclosed ties to the biopharmaceutical industry, including AstraZeneca, which funded the study.