Researchers at the Icahn School of Medicine at Mount Sinai have developed a groundbreaking method to generate billions of rare immune cells known as conventional type I dendritic cells (cDC1s). This advancement, detailed in a recent study published in Cancer Immunology Research, may lead to a new class of off-the-shelf cellular cancer vaccines, significantly impacting the treatment landscape for various cancers.
cDC1s are crucial for triggering and sustaining immune responses against tumors. Historically, these cells are scarce in the human body, making them challenging to isolate in large quantities. The innovative serum-free culture system created by the research team allows for the production of nearly 3 billion functional cDC1s from just 1 million hematopoietic stem cells (HSCs) obtained from cord blood—an unprecedented achievement in cancer research.
Transformative Potential for Cancer Treatment
“This is a major step toward the creation of universal cell-based cancer vaccines,” stated Nina Bhardwaj, MD, Ph.D., the study’s senior author and Director of the Vaccine and Cell Therapy Laboratory at Mount Sinai. She emphasized the difficulties in obtaining cDC1s at scale, noting that the team has now overcome this barrier.
Unlike other dendritic cells, cDC1s have a unique ability to cross-present tumor antigens, which is essential for activating cancer-fighting T cells. Their presence within tumors correlates strongly with improved patient outcomes and successful responses to immune checkpoint inhibitors, although their quantity and functionality are frequently reduced 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,” explained Sreekumar Balan, Ph.D., the corresponding author and Assistant Professor of Medicine at Mount Sinai. This breakthrough opens avenues for creating off-the-shelf cellular vaccines that could be broadly applicable across various cancer types.
Research Validation and Implications
The research, conducted in collaboration with the Mater Research Institute in Brisbane, Australia, utilized humanized mouse models to validate the functionality of lab-grown cDC1s as a cancer vaccine. This study marks the first successful demonstration of scalable production of bona fide, functional human cDC1s through a serum-free protocol.
The researchers generated nearly 3 billion cDC1s from just 1 million cord blood-derived HSCs. These cells not only maintained their identity and purity but also exhibited critical immune functions, including efficient antigen cross-presentation and T cell activation, demonstrating their potential as a vaccine platform. When tested in vivo in humanized tumor models, the cDC1s elicited strong anti-tumor immune responses.
The implications of this research are profound. It lays the groundwork for developing a new type of cancer immunotherapy—a universal off-the-shelf cellular vaccine that leverages the body’s immune system to combat cancer. Given that cDC1s are central to initiating robust T cell responses, this innovative approach could significantly enhance the effectiveness of existing treatments, including immune checkpoint inhibitors.
Moreover, the method offers researchers an unparalleled tool for studying the biology of cDC1s in both health and disease. This could lead to new insights regarding their role in immune surveillance and tumor resistance.
“This is not just about scaling up a cell type,” Dr. Bhardwaj added. “It’s about transforming how we design immune therapies, making them more effective, accessible, and personalized.”
For further details, refer to the study by Sreekumar Balan et al., titled “Harnessing Notch Signaling to Enhance the Generation and Functionality of Human Conventional Type I Dendritic Cells for Cancer Immunotherapy Applications,” published in Cancer Immunology Research (2025). DOI: 10.1158/2326-6066.CIR-25-0034.
