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
News
Our books now available worldwide!
Online Sellers other than Amazon, Routledge, and IOPP Indigo Global Health Care Equivalency in the Age of Nanotechnology, Nanomedicine and Artifcial Intelligence Global Health Care Equivalency In The Age Of Nanotechnology, Nanomedicine And Artificial [...]
Scientists Discover Why Some COVID Survivors Still Can’t Taste Food Years Later
A new study provides the first direct biological evidence explaining why some people continue to experience taste loss long after recovering from COVID-19. Researchers have uncovered specific biological changes in taste buds that could help [...]
Catching COVID significantly raises the risk of developing kidney disease, researchers find
Catching Covid significantly raises the risk of developing deadly kidney disease, research has shown. The virus was found to increase the chances that patients will develop the incurable condition by around 50 per cent. [...]
New Toothpaste Stops Gum Disease Without Harming Healthy Bacteria
Researchers have developed a targeted approach to combat periodontitis without disrupting the natural balance of the oral microbiome. The innovation could reshape how gum disease is treated while preserving beneficial bacteria. The human mouth [...]
Plastic Without End: Are We Polluting the Planet for Eternity?
The Kunming Montreal Global Biodiversity Framework calls for the elimination of plastic pollution by 2030. If that goal has been clearly set, why have meaningful measures that create real change still not been implemented? [...]
Scientists Rewire Natural Killer Cells To Attack Cancer Faster and Harder
Researchers tested new CAR designs in NK-92 cells and found the modified cells killed tumor cells more effectively, showing stronger anti-cancer activity. Researchers at the Ribeirão Preto Blood Center and the Center for Cell-Based [...]
New “Cellular” Target Could Transform How We Treat Alzheimer’s Disease
A new study from researchers highlights an unexpected player in Alzheimer’s disease: aging astrocytes. Senescent astrocytes have been identified as a major contributor to Alzheimer’s progression. The cells lose protective functions and fuel inflammation, particularly in [...]
Treating a Common Dental Infection… Effects That Extend Far Beyond the Mouth
Successful root canal treatment may help lower inflammation associated with heart disease and improve blood sugar and cholesterol levels. Treating an infected tooth with a successful root canal procedure may do more than relieve [...]
Microplastics found in prostate tumors in small study
In a new study, researchers found microplastics deep inside prostate cancer tumors, raising more questions about the role the ubiquitous pollutants play in public health. The findings — which come from a small study of 10 [...]
All blue-eyed people have this one thing in common
All Blue-Eyed People Have This One Thing In Common Blue Eyes Aren’t Random—Research Traces Them Back to One Prehistoric Human It sounds like a myth at first — something you’d hear in a folklore [...]
Scientists reveal how exercise protects the brain from Alzheimer’s
Researchers at UC San Francisco have identified a biological process that may explain why exercise sharpens thinking and memory. Their findings suggest that physical activity strengthens the brain's built in defense system, helping protect [...]
NanoMedical Brain/Cloud Interface – Explorations and Implications. A new book from Frank Boehm
New book from Frank Boehm, NanoappsMedical Inc Founder: This book explores the future hypothetical possibility that the cerebral cortex of the human brain might be seamlessly, safely, and securely connected with the Cloud via [...]
Deadly Pancreatic Cancer Found To “Wire Itself” Into the Body’s Nerves
A newly discovered link between pancreatic cancer and neural signaling reveals a promising drug target that slows tumor growth by blocking glutamate uptake. Pancreatic cancer is among the most deadly cancers, and scientists are [...]
This Simple Brain Exercise May Protect Against Dementia for 20 Years
A long-running study following thousands of older adults suggests that a relatively brief period of targeted brain training may have effects that last decades. Starting in the late 1990s, close to 3,000 older adults [...]
Scientists Crack a 50-Year Tissue Mystery With Major Cancer Implications
Researchers have resolved a 50-year-old scientific mystery by identifying the molecular mechanism that allows tissues to regenerate after severe damage. The discovery could help guide future treatments aimed at reducing the risk of cancer [...]
This New Blood Test Can Detect Cancer Before Tumors Appear
A new CRISPR-powered light sensor can detect the faintest whispers of cancer in a single drop of blood. Scientists have created an advanced light-based sensor capable of identifying extremely small amounts of cancer biomarkers [...]
