Transgenic T cells against malignant brain tumors
New form of therapy tested
Glioblastomas are the most aggressive of all brain tumors. They spread diffusely in the brain and are difficult to remove completely by surgery. Chemotherapy or radiation therapy also often have limited effectiveness. To find new, more effective treatment options for those affected, doctors and scientists are testing numerous immunotherapeutic approaches, including so-called "adoptive" T-cell therapies: This involves isolationg T cells from the patient, modifying them in the culture dish and transferring them back to the patient. Doctors are pursuing a variety of approaches.
Lukas Bunse, a scientist at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) and a physician at the University Medical Center Mannheim, relies on the comparatively new concept of "T cell receptor transgenic cells" in his current study: To this end, brain tumor patients were first inoculated with an antigenic fragment of the protein NLGN4X (Neuroligin4X). This protein is involved in the formation of synapses. It is found in large quantities in glioblastoma cells, but is virtually undetectable in healthy brain tissue.
Bunse's team then isolated from the blood of the vaccinated individuals those T cells that had been activated by NLGN4X and consequently carried a T cell receptor that specifically "recognizes" this glioblastoma-associated antigen.
However, since only a few NLGN4X-specific T cells can be obtained in this way, which are not sufficient for cell therapy, the scientists resorted to a trick: they isolated the gene coding for the NLGN4X-specific T cell receptor. They were then able to use this to equip T cells from donor blood or also T cell lines in the culture dish. In this way, they succeeded in producing large numbers of T cells with identical specificity, all of which recognize the cancer antigen NLGN4X.
Bunse's team then demonstrated that the NLGN4X-specific T cells are able to kill brain tumor cells in the culture dish. Brain tumor-bearing mice treated with transgenic NLGN4X-specific human T cells had a greater than 40 percent response to treatment. The tumors shrank and the animals survived longer than untreated conspecifics.
After these initial studies had yielded such promising results, Lukas Bunse expects that vaccine-induced T-cell receptors targeting brain tumor antigens could be a promising approach to develop new immunotherapies against glioblastoma. In melanoma, the malignant black skin cancer, such T-cell receptor transgenic T cells have already been shown to prolong the lives of some patients. According to the scientist, it is also conceivable to generate T cell receptor transgenic cell therapies against patient-individual cancer antigens.
Much more advanced in clinical development than T-cell receptor transgenic cells are cellular therapies using so-called CAR-T (chimeric antigen receptor) cells, which have already been approved for the treatment of various leukemias and lymphomas. But the two cell therapy approaches differ in one important respect. "With the T-cell receptor transgenic cells, we can also target antigens that are only found inside cancer cells and whose fragments are exhibited on the cell surface via presentation molecules known as MHC class 1," explains Lukas Bunse. This is not possible with the receptor of the CAR-T cells.
Michael Platten, director of the Department of Neurology at the University Medical Center Mannheim and department head at the German Cancer Research Center, sums up, "We will now work intensively to be able to test this concept in the clinic."
Other news from the department science
PicoRuler: Molecular Rulers for High-Resolution Microscopy
Opening the Door to Investigate Complex Processes in Cells
Taking antibiotics back in time
“Recreating such an ancient molecule was exhilarating, akin to bringing dinosaurs or wooly mammoths back to life”
X-ray laser uncovers the structure of a natural anti-mosquito insecticide
Bacterial protein found to work against more species of mosquito as previously thought
Researchers Decipher Enzyme Scissors of Intestinal Microbes
Intestinal bacteria utilise so-called beta-elimination to break down plant natural products and thus make them available to humans
Risk of serious COVID-19 infection can now be predicted
Researchers develop rapid test for severe infections
Children, pregnant women and breastfeeding mothers should avoid Brazil nuts
Brazil nuts can contain unusually high levels of radioactive radium
New approach to the sensible utilisation of carbon dioxide from car exhaust gases
"A method has been discovered that uses impure CO2 streams and enables a breakthrough in the synthesis of valuable chemicals and pharmaceuticals"
Boosting PET recycling with higher standards for laboratory experiments
New study shows how enzymatic plastic degradation could be brought one step closer to commercialisation
Seeing cancer’s spread through a computational window
Computational model allows researchers to simulate cellular-scale interactions across unprecedented distances in the human vasculature
Artificial intelligence finds ways to develop new drugs
The chemists tested the process using borylation – a reaction that activates hydrocarbon scaffolds
Could eating turkey ease colitis?
According to data in mice, extra tryptophan could reduce the risk of future colitis flares
Physicists observed random loops in chromosomes and revealed how loops affect spatial organization of genome
Luxembourg discovery advances Parkinson’s disease diagnosis
Scientists uncover paradigm-shifting immune cell markers for early Parkinson's detection with particular relevance to women
Most read news
Bowel cancer: aspirin activates protective genes
Researchers have identified a signaling pathway by which aspirin can inhibit colorectal cancer.
New drug delivery system could reduce daily diabetes shots to just three a year
Dietary management drugs have transformed Type 2 diabetes care, but daily injection routines are challenging for some patients
How stem cells and immune cells communicate
Lisec Artz Award for Simon Haas: Groundbreaking discovery of an unknown protective mechanism against blood cancer from stem cells
The weight of pollution: exposure linked to obesity
Chronic exposure to environmental pollutants found to increase risk of cardiovascular disease
Textbook knowledge turned on its head: 3-in-1 microorganism discovered
Newly multifunctional bacterial species
Plastic-eating bacteria turn waste into useful starting materials for other products
Microbial Upcycling of Waste PET
More news from our other portals
New designs for solid-state electrolytes may soon revolutionize the battery industry
Scientists achieve monumental improvements in lithium-metal-chloride solid-state electrolytes
Dunning-Kruger effect with muesli bars
Those who know the least consider themselves highly competent
Autonomous measuring instruments systematically detect new materials
A new algorithm measures materials libraries up to four times faster than before: It’s based on machine learning
Dow and Evonik announce startup of hydrogen peroxide to propylene glycol (HPPG) pilot plant
Innovative technology offer flexibility, lower costs, and a smaller environmental footprint
Naked Clams: The New Superfood Sensation Emerging from the Depths
Researchers found Naked Clams contain almost twice the amount of Vitamin B12 as blue mussels and have developed an efficient way to farm them
Aston University technology to combat the not-so sweet practice of honey fraud
Light technology to be used to detect if honey is blended with cheap additions
This is a battery
Two colored liquids bubbling through tubes: Is this what the battery of the future looks like?
Pushers, overcrowded trains and phone zombies
Sprite presents the world's first vending machine that responds to the things that bother Generation Z the most
Researchers discover new ultra strong material for microchip sensors
A material that doesn't just rival the strength of diamonds and graphene, but boasts a yield strength 10 times greater than Kevlar
Inauguration of the world’s first pilot plant for the cost-efficient production of green methanol
Start-up C1 Green Chemicals AG and research partners develop fundamentally new production process
Converting PFAS “forever chemicals” into valuable compounds
Scientists develop a new method to incorporate harmful perfluoroalkenes into N-heterocyclic carbene ligands
Graphene's proton permeability: A switch for future energy technologies
This discovery could lead to the development of more efficient hydrogen fuel cells and solar water-splitting devices
From the trough to the plate - digitally calculated
Computer program "ConTrans" estimates how much of an undesirable substance is transferred from animal feed to food
‘Hot’ new form of microscopy examines materials using evanescent waves
“This microscope technology is completely new, so we’re still learning specifically how and where it can be applied”
Lithium-ion batteries are no longer the gold standard in battery tech
On the way to safer and more powerful energy sources
Not so silver lining: Microplastics found in clouds could affect the weather
Low-altitude and denser clouds contained greater amounts of microplastics
Tönnies Group launches first nationwide "Meat Climate Platform"
100 guests at the Future Forum for Agriculture
CO2-free hydrogen: BASF receives funding approval for 54-megawatt water electrolysis plant
Proton exchange membrane (PEM) electrolyzer expected to produce up to 8,000 metric tons of hydrogen per year
Making molecules faster: Discovery dramatically reduces time it takes to build molecules
AI and human touch combine to revolutionize chemical synthesis