In a breakthrough study published in Cancer Immunology Research , scientists at the Icahn School of Medicine at Mount Sinai have developed a novel method to generate billions of rare immune cells known as conventional type I dendritic cells (cDC1s), potentially paving the way for a new class of off-the-shelf cellular cancer vaccines.
These dendritic cells play a central role in triggering and sustaining immune responses against tumors. They are notoriously scarce in the human body and difficult to isolate in large numbers. The Mount Sinai team's new serum-free culture system enables the production of nearly 3 billion functional cDC1s from just 1 million hematopoietic stem cells (HSCs) derived from cord blood—a feat never before achieved.
"This is a major step toward the creation of universal cell-based cancer vaccines," said senior author Nina Bhardwaj, MD, PhD, Ward-Coleman Chair in Cancer Research and Director of the Vaccine and Cell Therapy Laboratory at the Icahn School of Medicine at Mount Sinai. "Conventional type I dendritic cells are essential for mobilizing the immune system to fight cancer, but they're almost impossible to obtain at scale. We've now overcome that barrier."
Unlike other types of dendritic cells, cDC1s possess a unique ability to cross-present tumor antigens, an essential mechanism for activating cancer-fighting T cells. Their presence in tumors strongly correlates with better patient outcomes and successful response to immune checkpoint inhibitors. However, their quantity and function are often diminished in cancer patients.
"Our method not only expands cDC1s in large numbers, but also retains their ability to stimulate strong anti-tumor immunity in preclinical models," said Sreekumar Balan, PhD, corresponding author of the study and Assistant Professor of Medicine (Hematology and Medical Oncology) at the Icahn School of Medicine. "This opens the door to designing off-the-shelf cellular vaccines that could be broadly applicable across many cancer types."
The research, conducted in collaboration with the Mater Research Institute in Brisbane, Australia, used humanized mouse models to validate the ability of lab-grown cDC1s to function as a cancer vaccine.
The study presents the first demonstration of scalable production of bona fide, functional human cDC1s using a serum-free protocol. Researchers successfully generated nearly 3 billion cDC1s from just one million cord blood-derived HSCs. Not only did these cells maintain their identity and purity, but they also demonstrated critical immune functions—including efficient antigen cross-presentation and the ability to activate T cells—making them highly effective as a vaccine platform. These cDC1s were then tested in vivo in humanized tumor models, where they showed the ability to elicit strong anti-tumor immune responses.
The implications of this work are wide-reaching. First, it lays the foundation for developing a new type of cancer immunotherapy: a universal off-the-shelf cellular vaccine that harnesses the body's own immune system to fight cancer. Because cDC1s are central to initiating robust T cell responses, this approach could dramatically enhance the effectiveness of existing treatments, such as immune checkpoint inhibitors, and be tailored for use across various malignancies. Second, the method provides researchers with an unprecedented tool to study the biology of cDC1s in both health and disease, helping to unlock new insights into their role in immune surveillance and tumor resistance.
"This is not just about scaling up a cell type," added Dr. Bhardwaj. "It's about transforming how we design immune therapies, making them more effective, accessible, and personalized."
This study received funding from the Waldman Melanoma Research Fund and the Antidote Health Foundation For Cure of Cancer. With contributions from Mount Sinia's Xuedi Wang, Christopher McClain, and Antes Peros.
About the Icahn School of Medicine at Mount Sinai
The Icahn School of Medicine at Mount Sinai is internationally renowned for its outstanding research, educational, and clinical care programs. It is the sole academic partner for the seven member hospitals* of the Mount Sinai Health System, one of the largest academic health systems in the United States, providing care to New York City's large and diverse patient population.
The Icahn School of Medicine at Mount Sinai offers highly competitive MD, PhD, MD-PhD, and master's degree programs, with enrollment of more than 1,200 students. It has the largest graduate medical education program in the country, with more than 2,600 clinical residents and fellows training throughout the Health System. Its Graduate School of Biomedical Sciences offers 13 degree-granting programs, conducts innovative basic and translational research, and trains more than 560 postdoctoral research fellows.
Ranked 11th nationwide in National Institutes of Health (NIH) funding, the Icahn School of Medicine at Mount Sinai is among the 99th percentile in research dollars per investigator according to the Association of American Medical Colleges. More than 4,500 scientists, educators, and clinicians work within and across dozens of academic departments and multidisciplinary institutes with an emphasis on translational research and therapeutics. Through Mount Sinai Innovation Partners (MSIP), the Health System facilitates the real-world application and commercialization of medical breakthroughs made at Mount Sinai.
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* Mount Sinai Health System member hospitals: The Mount Sinai Hospital; Mount Sinai Brooklyn; Mount Sinai Morningside; Mount Sinai Queens; Mount Sinai South Nassau; Mount Sinai West; and New York Eye and Ear Infirmary of Mount Sinai.
