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Immunotherapy: use cancer cells for their treatment themselves


New approach to immunotherapy directly from the cancer cell

When treating cancer, doctors place great hope in what is known as immunotherapy, which is supposed to target the body's defenses against the cancer cells. Scientists from the National Center for Tumor Diseases (NCT) Heidelberg, the German Cancer Research Center and the University Hospital Heidelberg (UKHD) have now made significant progress. With the help of measles viruses, they had cancer cells produce bispecific antibody fragments, so-called “BiTEs” (bispecific T cell engagers).

"Therapy approaches that use the body's defense are becoming increasingly important in cancer treatment"; explain the scientists of the NCT. One of these new methods is the use of the “BiTEs”, which connect T cells with the tumor cells and thus trigger the programmed cell death of the cancer cell. Here, the researchers have now developed a method in which cancer cells themselves produce the antibody fragments. In this way, the BiTEs can be formed directly in the tumors, which promises better treatment results with fewer side effects. The researchers have published their results in the journal "Clinical Cancer Research".

BiTE therapy already available for blood cancer

According to the experts, the bispecific antibody fragments have so far only been used successfully in a few types of blood cancer and the treatment is sometimes associated with serious side effects. The artificially produced BiTEs consist of the binding regions of two antibodies, each of which “recognizes” different target structures, according to the NCT. One of the two binding sites remains the same for all BiTEs and is reserved for the protein CD3, which is found on the T cells. The second binding region is varied in a tumor-specific manner. The BiTEs ensure that the T cells are directed to the tumor cell and trigger programmed cell death there.

Impending serious side effects with previous therapy

Although effective BiTEs are already in use against certain forms of leukemia, the antibody fragments have so far not been used against solid tumors such as skin or colon cancer, says NCT cancer researcher Christine Engeland. In addition, there is the problem that the "BiTEs have so far been administered as a continuous infusion" and "serious, sometimes life-threatening side effects can occur"; explains the expert.

Modified measles viruses help with BiTE production

In the search for possible approaches to improve BiTE treatment, the scientists in Guy Unjust's Virotherapy working group at the NCT Heidelberg used weakened measles viruses, which were modified so that the bispecific antibody fragments were then formed directly in the tumors. In experiments on mice, they were able to demonstrate that the modified weakened measles viruses do not trigger a disease, but that they multiply in tumor cells, so that the BiTEs are subsequently produced there by the cancer cells themselves.

Significantly fewer side effects

"The advantage of the procedure is that no BiTEs get into the bloodstream and side effects are avoided," emphasizes Christine Engeland. According to the scientists, the risk of side effects when using the method was very low and there were no signs of toxicity. In addition, virus multiplication in the tumor stimulates the body's immune system, which makes the immune system aware of the cancer, so to speak.

Success also in skin and colon cancer

In the experiments on mice, doctoral students Tobias Speck and Johannes Heidbüchel were also able to show that treatment with BiTE viruses in skin and colon cancer significantly extended survival and even brought about healing in some animals. NCT expert Christine Engeland now hopes "that the new therapy concept will also be an effective strategy in the treatment of tumors in humans." To check this, however, further investigations are required, which the scientists would like to start this year. (fp)

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