Engineered Immune Cells Pave the Way for New Off-the-Shelf Cancer Vaccines

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.” 

Reference: Balan S, O’Brien L, Peros A, et al. Harnessing notch signaling to enhance the generation and functionality of human conventional type I dendritic cells for cancer immunotherapy applications. Cancer Immunol Res. 2025. doi: 10.1158/2326-6066.CIR-25-0034

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