Cancer immunotherapy transforms a patient’s immune cells into a “search‑and‑destroy” force against tumors. But many cancers learn to camouflage themselves from dendritic cells—the immune system’s scouts—making them harder to detect and target.
Dendritic cells normally collect tumor antigens and present them to T cells, which then attack cancer cells. Clinicians have tried to overcome tumor evasion by harvesting dendritic cells from patients, loading them with tumor antigens in the lab, and reinfusing them in an effort to train dendritic cells to better identify the tumor. Yet this approach is limited: lab‑grown dendritic cells often lack key activation molecules, and the antigens supplied ex vivo represent only a fraction of those present in tumors.
Tumor cells release extracellular vesicles (EVs)—tiny packets carrying proteins and antigens. If dendritic cells could capture these vesicles inside the body, they might trigger more precise and effective immune responses. Researchers at the Ecole Polytechnique Fédérale de Lausanne (EPFL), led by Michele De Palma, PhD, have developed two bioengineering strategies to exploit EVs and enhance dendritic‑cell immunotherapy.
In work published in Nature Communications in October 2025 titled, “Dendritic cell progenitors engineered to express extracellular-vesicle–internalizing receptors enhance cancer immunotherapy in mouse models,” the team introduced the EV‑internalizing receptor (EVIR) into dendritic cell progenitors. EVIR enabled dendritic cells to efficiently take up tumor‑derived EVs and present their antigens to T cells. In mouse models of melanoma resistant to mainstream immunotherapy, EVIR‑engineered dendritic cells elicited robust immune responses and slowed tumor growth.
Building on this foundation, a new paper titled “Coordinate tumor-antigen uptake and dendritic cell activation by chimeric antigen receptors,” published in Science Translational Medicine, describes an engineered, ubiquitination-resistant instructive chimeric antigen receptor (iCAR). The authors explain that iCAR‑engineered dendritic cells can recognize molecules on cancer cells or their extracellular vesicles—such as GD2 in melanoma or HER2 in epithelial tumors—promoting antigen uptake. They also activate to prime antigen-specific T cells through cross‑dressing and cross‑presentation and induce cytokine interleukin-12 (IL-12) expression in response to antigen capture. In preclinical melanoma models, iCAR‑engineered dendritic cells delayed tumor progression and expanded T‑cell diversity—without requiring ex vivo antigen loading or maturation.
Together, these advances bring dendritic‑cell engineering into the preclinical realm, demonstrating proof of concept for antigen‑agnostic immunotherapy. By integrating antigen uptake with programmable dendritic cell activation, EVIR and iCAR platforms may overcome longstanding limitations of dendritic‑cell‑based therapies.
Ali Ghasemi, PhD, and Yahya Mohammadzadeh, PhD—both former doctoral students on the project—have co‑founded EVIR Therapeutics, a biotechnology startup focused on advancing engineered dendritic‑cell therapies into clinical applications. The company will focus on engineered dendritic cells designed for improved performance in vivo, bridging the gap between laboratory breakthroughs and patient care. De Palma added, “Our goal is to relaunch the clinical potential of dendritic-cell-based therapies through engineering them for improved performance in vivo—enhanced antigen uptake coupled to cell activation, without the need for antigen exposure ex vivo.”
