Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

More Cancer-Fighting Power – Mouse with Highly Effective Components of the Human Immune System

09.08.2010
How to make the immune system more potent against cancer? Researchers of the Max Delbrück Center (MDC) and Charité Universitätsmedizin in Berlin, Germany, have dedicated ten years of research to modify T cell receptors (TCRs), the antenna-like structures of T cells, so that that they would no longer ignore cancer cells, but instead specifically track and recognize them. This modification is the precondition for the immune system to destroy cancer cells. The researchers developed a mouse with a whole repertoire of these human T cell receptors (Nature Medicine, doi: 10.1038/nm.2197)* with the aim of utilizing these receptors in the future for targeted immunotherapy in patients.

The T cells of the immune system possess receptors on their surface with which they can recognize bacteria, viruses, and fungi and which enable the immune system to fight against foreign invaders and destroy them. At the same time, however, T cells must differentiate between “self” and “foreign” – between the body’s own proteins and foreign proteins – so that the immune system tolerates the body’s own tissue. If the immune system is no longer able to make this differentiation, it attacks “self” structures, leading to autoimmune diseases such as type 1 diabetes or multiple sclerosis.

In cancer diseases, however, the immune system appears to be restricted in its response. Cancer cells originate from the body’s own tissue, which is why the immune system obviously has trouble recognizing them – and that, although cancer cells often have antigens (from the Greek word antigennan meaning “produce against”) which make them recognizable as tumor cells and pathologically altered cells.

Professor Thomas Blankenstein and his research team at the MDC and Charité want to break this tolerance towards cancer cells. In their research they utilized a process which in mammals automatically makes mature immune cells out of immature T cells. Immature T cells do not yet possess any T cell receptors and thus have to migrate from the bone marrow to the thymus. In this gland, which is part of the immune system, the T cell receptor genes, with which the T cell recognizes antigens, undergo random gene rearrangement.

Each of the millions of generated T cells expresses only one T cell receptor on the cell surface with which an antigen is recognized. In the thymus, however, all T cells which recognize “self” structures are deactivated. T cells which specifically target foreign antigens are spared from these tolerance mechanisms. The mouse, for example, does not develop any tolerance toward human cancer cell antigens.

“Probably no other transgenic mouse has that many human gene segments”
T cell receptors (TCR) consist of an alpha and a beta chain. Professor Blankenstein and his research team increased the DNA building blocks of humans for these chains with the aid of an artificial chromosome (YAC - yeast artificial chromosome) and then introduced them into embryonic stem cells of the mouse. Altogether there were approximately 2 million DNA building blocks, corresponding to 2 megabases or around 170 gene segments. “Probably no other transgenic mouse has that many human gene segments,” said Professor Blankenstein.
Transgenic mouse with human T cell receptors
In ten years of developmental work the researchers in Berlin used embryonic stem cells loaded with human DNA to breed transgenic mice, which possess all possible human T cell receptors on their T cells. “These human T cell receptors in the mouse recognize human antigens of human cancer cells. For the mice human tumor antigens are foreign,” Professor Blankenstein explained. “Such highly effective T cell receptors do not exist in humans. They are destroyed in humans in order to prevent them from attacking the body’s own structures. Only T cells remain with less effective T cell receptors,” he stressed.

The researchers aim to isolate these high-affinity human T cell receptors of the mouse, for which human cancer antigens are foreign, and to introduce them into the T cells of cancer patients. In this way the patients’ ineffective T cells shall be boosted in their effectiveness to destroy the cancer cells. In contrast to a bone marrow transplantation, in which many T cells of the transplant are activated in the recipient, which can lead to life-threatening destruction of healthy cells, this therapy approach is very selective. With this method the researchers hope to avoid an overreaction of the immune system.

Whether the highly upgraded human T cells from the mouse preserve their great effectiveness in humans remains to be seen. At present the researchers are preparing a first clinical trial, in which they will test the effectiveness and tolerance of these T cell receptors in cancer patients.

Professor Blankenstein is also spokesperson of the transregional collaborative research program “Principles and Applications of Adoptive T Cell Therapy” in Berlin and Munich. This program, funded by the German Research Foundation until 2014, explores new approaches to cancer treatment with the aid of the immune system. Participants in this program along with the MDC and the Charité in Berlin are the German Rheumatism Research Center Berlin and in Munich the Helmholtz Zentrum München – German Research Center for Environmental Health and two universities, Technische Universität München (TUM) and Ludwig-Maximilians-Universität (LMU).

A photo and graphics can be downloaded from the internet at:
http://www.mdc-berlin.de/de/index.html
*Transgenic mice with a diverse human T-cell antigen receptor repertoire
Liang-Ping Li1,2*, J. Christoph Lampert1,2*, Xiaojing Chen1,2, Catarina Leitao1,2, Jelena Popoviæ1,2, Werner Müller3 and Thomas Blankenstein1,2
1 Max Delbrück Center for Molecular Medicine, Robert-Rössle Strasse 10, 13092 Berlin, Germany
2 Institute of Immunology, Charité Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany

3 Bill Ford Chair in Cellular Immunology, University of Manchester, Faculty of Life Sciences, Oxford Road, Manchester, M13 9PT

*These authors contributed equally to this work

Barbara Bachtler
Press and Public Affairs
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Robert-Rössle-Straße 10; 13125 Berlin; Germany
Phone: +49 (0) 30 94 06 - 38 96
Fax: +49 (0) 30 94 06 - 38 33
e-mail: presse@mdc-berlin.de
Claudia Peter
Stv. Leiterin Unternehmenskommunikation
Charité - Universitätsmedizin Berlin
Charitéplatz 1
10117 Berlin
Phone: +49-(0) 30 450 570 - 503
Fax: +49-(0) 30 450 570 - 940
e-mail: Claudia.Peter@charite.de

Barbara Bachtler | Max-Delbrück-Centrum
Further information:
http://www.charite.de/
http://www.mdc-berlin.de/
http://www.sfb-tr36.com/

More articles from Life Sciences:

nachricht Ambush in a petri dish
24.11.2017 | Friedrich-Schiller-Universität Jena

nachricht Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New proton record: Researchers measure magnetic moment with greatest possible precision

High-precision measurement of the g-factor eleven times more precise than before / Results indicate a strong similarity between protons and antiprotons

The magnetic moment of an individual proton is inconceivably small, but can still be quantified. The basis for undertaking this measurement was laid over ten...

Im Focus: Frictional Heat Powers Hydrothermal Activity on Enceladus

Computer simulation shows how the icy moon heats water in a porous rock core

Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

IceCube experiment finds Earth can block high-energy particles from nuclear reactions

24.11.2017 | Physics and Astronomy

A 'half-hearted' solution to one-sided heart failure

24.11.2017 | Health and Medicine

Heidelberg Researchers Study Unique Underwater Stalactites

24.11.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>