Mouse With Components of the Human Immune System

Photo: Mouse

Transgenic mice with a diverse hu-
man T-cell antigen receptor repertoire;
© SFB-TR 36

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 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 invaders and which enable the immune system to fight and destroy them. At the same time, however, T cells must differentiate between between the body’s own proteins and foreign proteins – so that the immune system tolerates the body’s own tissue.

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 which make them recognizable as tumor cells and pathologically altered cells.

Professor Thomas Blankenstein and his team 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.

Professor Blankenstein and his research team increased the DNA building blocks of humans into embryonic stem cells of the mouse. “Probably no other transgenic mouse has that many human gene segments,” said Blankenstein.

“These human T cell receptors in the mouse recognize human antigens of human cancer cells. For the mice human tumor antigens are foreign,” 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.


MEDICA.de; Source: Max-Delbrück-Centrum für Molekulare Medizin (MDC) Berlin-Buch