However, the T cells not only kill cancer cells – they additionally destroy the tumor blood vessel system, thus impeding the supply of nutrients to the tumor. Consequently, “escapee” mutant tumor cells are eradicated that have become resistant to drug-based treatment and are responsible for tumor recurrence. (Cancer Cell, doi10.1016/j.ccr.2011.10.019)*.
The researchers transplanted tumor cells into mice that express SV40 large T antigen (Tag), the oncogene that is critical for tumor growth. The researchers were thus able to target and inactivate the oncogene using the antibiotic drug doxycycline (dox), which has an effect similar to modern drugs currently in clinical use. Since the oncogene is also present as antigen on the surface of the tumor cells, the researchers were also able to target these tumors with oncogene-specific T cells. Thus, for the first time the effect of the two completely different therapy approaches could be compared directly with each other.
Moreover, a special feature of the study was that the tumors in the mice were large – bigger than one centimeter and containing about one billion cancer cells, comparable to clinical-size tumors in patients. Only then, according to the researchers, is the development of the tumor tissue (tumor stroma), which also includes the tumor vasculature, complete. The tumor is then considered “established”. The aim of tumor therapy is to kill all cancer cells to prevent the recurrence of cancer disease.
The researchers showed in mice that the tumor is destroyed by the drug-mediated inactivation of the oncogene, but that the tumor vasculature and thus the blood supply of the tumor remains intact. In addition, due to a high mutation rate, some cancer cells become resistant to the drug and quickly generate new tumors despite continual administration of the anti-cancer drug.
Adoptive T-cell therapy, the researchers noted, is more effective in the mice in the long term, because it destroys the blood supply of the tumor. In addition, it evidently intercepts cancer cells that have altered their characteristics via mutations and thus escape drug treatment. In adoptive T-cell therapy, the researchers modulate the cytotoxic T cells (immune cells toxic for the cell) in the test tube in such a way that the T cells recognize certain features on the surface of cancer cells and specifically destroy the tumor cells. Then these primed immune cells are transferred back into the mice. The researchers point out that techniques to produce highly specialized T cells against human tumors have recently been developed following previous studies by Professor Blankenstein’s research group. Now it will be important to determine exactly how these immune cells can be used in future clinical trials.
The researchers hope that their insights in defining optimal conditions for T cell therapy may help improve future clinical trials and thus the treatment of cancer patients.
*Oncogene-targeting T cells reject large tumors, while oncogene inactivation selects escape variants in mouse models of cancer
Kathleen Anders1, Christian Buschow2, Andreas Herrmann3, Ana Milojkovic4, Christoph Loddenkemper5, Thomas Kammertoens2, Peter Daniel4, Hua Yu3, Jehad Charo1, Thomas Blankenstein1,2,*1Max Delbrück Center for Molecular Medicine, 13092 Berlin, Germany
5Institute of Pathology, Charité Campus Benjamin Franklin, 12200, Berlin, GermanyContact:
Barbara Bachtler | Max-Delbrück-Centrum
Colorectal cancer risk factors decrypted
13.07.2018 | Max-Planck-Institut für Stoffwechselforschung
Algae Have Land Genes
13.07.2018 | Julius-Maximilians-Universität Würzburg
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
13.07.2018 | Event News
13.07.2018 | Materials Sciences
13.07.2018 | Life Sciences