Cancer biologists at EPFL, UNIGE, and the German Cancer Research Center (Heidelberg) have developed a novel immunotherapy that does not require knowledge of a tumor’s antigenic makeup. The new results may pave the way to first-in-kind clinical applications.
Unfortunately, tumors often erect barriers against the body’s immune system, allowing them to grow uncontrolled. This setback, called immunosuppression, may involve the inhibition of DCs and their ability to present tumor antigens to CD8+ T cells.
Addressing the limitations of traditional vaccines
Over the last few decades, researchers have worked to overcome tumor-induced immunosuppression by various strategies, collectively called immunotherapies, some of which are approved treatments effective in patients with certain cancers.
One approach is to generate DCs from the blood monocytes (a type of immune white blood cells) of a patient with cancer, expose them in the laboratory to defined tumor-derived material from a tumor biopsy (antigen loading step), and then reintroduce them into the patient’s body. This procedure, often referred to as a DC vaccine, is expected to significantly enhance the presentation of tumor antigens to CD8+ T cells.
However, DC vaccines have produced mixed results in clinical trials. One potential limitation is the use of monocyte-derived DCs. These cells lack certain essential properties of naturally occurring DCs, such as type I DCs (cDC1), which play a crucial role in activating CD8+ T cells.
Another potential shortcoming is its dependence on the antigen loading step, which uses predefined antigens that may not represent the full spectrum of relevant antigens present in cancer cells. Addressing the limitations of traditional DC vaccines could enhance their therapeutic efficacy.
A team of scientists led by Michele De Palma, associate professor in the School of Life Sciences and director of the Agora Cancer Research Center, has now developed engineered DCs with the capacity to differentiate into cDC1 and to stimulate anti-tumor immunity when transferred to mice with tumors, without the need for antigen loading step. The study is published in Nature Cancer.
“Our strategy does not use the monocyte-derived DCs employed in previous studies, but relies on a population of DC progenitors, called DCPs, which we can produce in vitro in the laboratory from readily available sources, such as blood and bone marrow,” De Palma explains.
Surpassing the outcomes
When engineered to express two immune-stimulatory molecules (IL-12 and FLT3L), the DCP could initiate effective anti-tumor immune responses in various cancer models, surpassing the outcomes achieved with other traditional DC formulations. “Remarkably, the engineered DCPs worked in the absence of antigen loading, which implies that they could be potentially effective against a broad range of human cancers, so irrespective of the antigens that they express.”
The ability of engineered DCPs to broadly engage multiple components of the immune system, not limited to CD8+ T cells, may explain their effectiveness. “A very promising result was the ability of the DCPs to unlock the efficacy of CAR-T cells in eradicating brain tumors in mice,” says Professor Denis Migliorini, head of neuro-oncology at UNIGE and one of the study’s authors.
CAR-T cells are another class of engineered immune cells already approved for the treatment of certain tumors, but their efficacy in brain cancer has so far been limited. “We are committed to combining DCPs with CAR-T cells in patients with incurable brain cancer,” adds Migliorini.
“Our preclinical results require further development and testing before moving to clinical application,” cautions De Palma. DCPs can be readily obtained from human blood, which should facilitate the translation of preclinical results into a potentially transformative cancer immunotherapy.
More information: Ali Ghasemi et al, Cytokine-armed dendritic cell progenitors for antigen-agnostic cancer immunotherapy, Nature Cancer (2023). DOI: 10.1038/s43018-023-00668-y
![](https://www.nanoappsmedical.com/wp-content/uploads/2017/05/spacer.jpg)
News
The Silent Battle Within: How Your Organs Choose Between Mom and Dad’s Genes
Research reveals that selective expression of maternal or paternal X chromosomes varies by organ, driven by cellular competition. A new study published today (July 26) in Nature Genetics by the Lymphoid Development Group at the MRC [...]
Study identifies genes increasing risk of severe COVID-19
Whether or not a person becomes seriously ill with COVID-19 depends, among other things, on genetic factors. With this in mind, researchers from the University Hospital Bonn (UKB) and the University of Bonn, in [...]
Small regions of the brain can take micro-naps while the rest of the brain is awake and vice versa
Sleep and wake: They're totally distinct states of being that define the boundaries of our daily lives. For years, scientists have measured the difference between these instinctual brain processes by observing brain waves, with [...]
Redefining Consciousness: Small Regions of the Brain Can Take Micro-Naps While the Rest of the Brain Is Awake
The study broadly reveals how fast brain waves, previously overlooked, establish fundamental patterns of sleep and wakefulness. Scientists have developed a new method to analyze sleep and wake states by detecting ultra-fast neuronal activity [...]
AI Reveals Health Secrets Through Facial Temperature Mapping
Researchers have found that different facial temperatures correlate with chronic illnesses like diabetes and high blood pressure, and these can be detected using AI with thermal cameras. They highlight the potential of this technology [...]
Breakthrough in aging research: Blocking IL-11 extends lifespan and improves health in mice
In a recent study published in the journal Nature, a team of researchers used murine models and various pharmacological and genetic approaches to examine whether pro-inflammatory signaling involving interleukin (IL)-11, which activates signaling molecules such [...]
Promise for a universal influenza vaccine: Scientists validate theory using 1918 flu virus
New research led by Oregon Health & Science University reveals a promising approach to developing a universal influenza vaccine—a so-called "one and done" vaccine that confers lifetime immunity against an evolving virus. The study, [...]
New Projects Aim To Pioneer the Future of Neuroscience
One study will investigate the alterations in brain activity at the cellular level caused by psilocybin, the psychoactive substance found in “magic mushrooms.” How do neurons respond to the effects of magic mushrooms? What [...]
Decoding the Decline: Scientific Insights Into Long COVID’s Retreat
Research indicates a significant reduction in long COVID risk, largely due to vaccination and the virus’s evolution. The study analyzes data from over 441,000 veterans, showing lower rates of long COVID among vaccinated individuals compared [...]
Silicon Transformed: A Breakthrough in Laser Nanofabrication
A new method enables precise nanofabrication inside silicon using spatial light modulation and laser pulses, creating advanced nanostructures for potential use in electronics and photonics. Silicon, the cornerstone of modern electronics, photovoltaics, and photonics, [...]
Caught in the actinium: New research could help design better cancer treatments
The element actinium was first discovered at the turn of the 20th century, but even now, nearly 125 years later, researchers still don't have a good grasp on the metal's chemistry. That's because actinium [...]
Innovative Light-Controlled Drugs Could Revolutionize Neuropathic Pain Treatment
A team of researchers from the Institute for Bioengineering of Catalonia (IBEC) has developed light-activated derivatives of the anti-epileptic drug carbamazepine to treat neuropathic pain. Light can be harnessed to target drugs to specific [...]
Green Gold: Turning E-Waste Into a Treasure Trove of Rare Earth Metals
Scientists are developing a process inspired by nature that efficiently recovers europium from old fluorescent lamps. The approach could lead to the long-awaited recycling of rare earth metals. A small molecule that naturally serves [...]
Cambridge Study: AI Chatbots Have an “Empathy Gap,” and It Could Be Dangerous
A new study suggests a framework for “Child Safe AI” in response to recent incidents showing that many children perceive chatbots as quasi-human and reliable. A study has indicated that AI chatbots often exhibit [...]
Nanoparticle-based delivery system could offer treatment for diabetics with rare insulin allergy
Up to 3% of people with diabetes have an allergic reaction to insulin. A team at Forschungszentrum Jülich has now studied a method that could be used to deliver the active substance into the [...]
Nanorobot kills cancer cells in mice with hidden weapon
Researchers at Karolinska Institutet in Sweden have developed nanorobots that kill cancer cells in mice. The robot's weapon is hidden in a nanostructure and is exposed only in the tumor microenvironment, sparing healthy cells. [...]