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”
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:
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 workBarbara Bachtler
Further reports about: > Blankenstein > Components > DNA > Human vaccine > Immune cell activation > Immunology > MDC > Mouse > T cell receptors > T cells > TCR > artificial chromosome > autoimmune disease > building block > cancer cells > cancer patients > cancer-fighting > embryonic stem > embryonic stem cell > healthy cell > immune cell > immune system > stem cells
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