However, the T cells not only kill cancer cells – they additionally destroy the tumour blood vessel system, thus impeding the supply of nutrients to the tumour. Consequently, “escapee” mutant tumour cells are eradicated that have become resistant to drug-based treatment and are responsible for tumour recurrence.
The researchers transplanted tumour cells into mice that express SV40 large T antigen (Tag), the oncogene that is critical for tumour 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 tumour cells, the researchers were also able to target these tumours 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 tumours in the mice were large – bigger than one centimetre and containing about one billion cancer cells, comparable to clinical-size tumours in patients. Only then, according to the researchers, is the development of the tumour tissue (tumour stroma), which also includes the tumour vasculature, complete. The tumour is then considered “established”. The aim of tumour therapy is to kill all cancer cells to prevent the recurrence of cancer disease.
The researchers showed in mice that the tumour is destroyed by the drug-mediated inactivation of the oncogene, but that the tumour vasculature and thus the blood supply of the tumour remains intact. In addition, due to a high mutation rate, some cancer cells become resistant to the drug and quickly generate new tumours 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 tumour. 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 recognise certain features on the surface of cancer cells and specifically destroy the tumour 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 tumours have recently been developed following previous studies by Blankenstein’s research group. Now it will be important to determine exactly how these immune cells can be used in future clinical trials.
MEDICA.de; Source: Max-Delbrück-Centrum für Molekulare Medizin (MDC) Berlin-Buch