A team of Cleveland researchers has found a way to turn the immune memory left behind by COVID-19 vaccination into an unlikely tool against cancer, using it to help the body recognize and attack tumors that normally hide from the immune system. The approach, called PROTEXI, is now headed toward its first human trials in sarcoma patients, a rare and often deadly cancer that starts in the body's connective tissues.
The findings, detailed in a study published in Nature Communications on July 27, come from a collaboration between Case Western Reserve University, University Hospitals, Celloram Inc. and MedPacto Inc., according to ACIR.org. As reported by Cleveland.com, University Hospitals is investigating the vaccine platform alongside Case Western Reserve and Celloram, with preliminary tests relying on immune cells drawn from donors who had been vaccinated against COVID-19.
Sarcoma, which includes cancers of the bones, nerves and blood vessels within the body's connective tissues, remains notoriously hard to treat once it spreads. The American Cancer Society estimates 13,910 new soft tissue sarcoma cases and 4,110 new bone cancer cases will be diagnosed nationwide in 2026, with sarcomas making up roughly 15% of all pediatric cancer diagnoses. The stakes of catching the disease early are stark: five-year survival for localized soft tissue sarcoma sits near 83% to 84%, but drops to just 31% once the cancer metastasizes to distant organs, according to the Sarcoma Foundation of America.
How Leftover Immunity Becomes an Anti-Cancer Weapon
PROTEXI works by loading a patient's own dendritic cells, the immune system's messenger cells, with personalized tumor antigens alongside fragments of the SARS-CoV-2 spike protein. Because so many people carry pre-existing CD4+ T-cell helper memory from COVID-19 infection or vaccination, the vaccine can borrow that memory to activate CD8+ cytotoxic T cells against tumors that would otherwise evade detection, according to Case Western Reserve University. Cleveland.com reports that the vaccine changed tumors typically able to slip past the immune system into ones more effectively recognized and attacked, and that it generated long-lasting immune memory that may help prevent recurrence.
Tej Pareek said the vaccine enhances cancer recognition by leveraging existing antiviral immune memory, per the same account from the outlet. Cleveland.com also reports that the vaccine strengthened the body's natural cancer-fighting defenses and worked better when combined with other immunotherapies.
Pairing the Vaccine With Other Cancer Drugs
In preclinical models, pairing PROTEXI with MedPacto's TGF-β inhibitor vactosertib or anti-PD-1 immune checkpoint inhibitors altered the tumor microenvironment and helped overcome treatment resistance in hard-to-treat tumors, according to the Seoul Economic Daily. TGF-β is a protein tumors produce to suppress immune attacks, and vactosertib is designed to block it. MedPacto's drug already carries FDA Fast Track designation, granted in January 2023, as a monotherapy for relapsed or refractory metastatic osteosarcoma.
The study published in Nature Communications suggested the treatment slowed tumor growth and improved survival, per the journal. Dr. John Letterio, director of the Angie Fowler Adolescent and Young Adult Cancer Institute at University Hospitals and co-leader at the Case Comprehensive Cancer Center, served as senior corresponding author on the work. Letterio, a professor of pediatrics at Case Western Reserve University and co-founder of Celloram Inc., is helping lead the push toward first-in-human clinical trials in sarcoma patients.
Cleveland's Growing Cell-Therapy Footprint
Celloram, the preclinical biotechnology company advancing PROTEXI toward those trials with University Hospitals, is headquartered in University Circle, Cleveland's primary medical and research district, according to Celloram. The company was formed to translate cell therapy platforms and small-molecule research into clinical applications. That work fits into a broader local push toward commercial translational medicine: University Hospitals and Case Western Reserve launched CDL-Cleveland in May, in partnership with Creative Destruction Lab, establishing what the hospital system describes as the first healthcare innovation stream anchored directly to a clinical hospital system.
PROTEXI is not the first therapeutic dendritic cell vaccine to reach this stage of development. Sipuleucel-T, sold as Provenge, was approved by the FDA in 2010 for advanced prostate cancer and remains the only FDA-approved therapeutic dendritic cell vaccine in the United States, according to Drug Discovery News. That vaccine demonstrated efficacy but its complex manufacturing process limited widespread adoption in oncology, a history that looms over any new dendritic cell platform trying to reach patients at scale.
Researchers still face a long road before PROTEXI could become an approved treatment. Moving from encouraging results in mouse models and donor cells to a validated therapy will require multiple phases of human clinical trials, and its ultimate usefulness may hinge on whether it continues to perform well alongside drugs like vactosertib or checkpoint inhibitors. For now, the planned sarcoma trials at University Hospitals mark the next step in testing whether Cleveland's approach to repurposing COVID-19 immunity can make a dent in a cancer that has long resisted treatment once it spreads.
