"Prehistoric relics" as targets for vaccination against cancer

Human endogenous retroviruses (HERV) entered the human genome millions of years ago and have been passed on from generation to generation. The human genome contains several thousand such endogenous retrovirus genes. As a rule, the genes of HERV are mute, i.e. they do not produce proteins. Researchers of the Paul-Ehrlich-Institut and other groups have already been able to show that an increase in expression of genes of one group of these retroviruses occurs in HIV infected individuals but also in the tumour cells of various types of cancer. The HERV group could be identified as HERV-K/HML-2(hom), or for short, HERV-K. Professor Dr Barbara Schnierle and her co-workers in the Virology Division of the Paul-Ehrlich-Institut now wanted to know whether the specific gene activity of HERV-K could be used therapeutically to fight cancer cells in a targeted manner. To protect healthy cells, it is required to identify structures as targets which are only displayed on cancer cells.

For their investigations, Professor Barbara Schnierle, head of the Section "AIDS, New and Emerging Pathogens", and her co-workers used a murine kidney cell line (Renca). This cell line had been genetically modified in such a way that the cells produced (human) HERV-K envelope proteins to emulate the situation of the HERV-positive human cancer cells as accurately as possible. Mice which received an i.v. administration of these cells developed lung metastases within a short period of time.

The murine renal carcinoma cell line Renca. On the left: without HERV-K envelope protein expression. On the right: genetically modified Renca cells with HERV-K envelope protein (in red). Source: PEI

For the "vaccination" against these tumours, the researchers used the modified vaccinia virus Ankara (MVA), an attenuated virus which cannot replicate after inoculation. In addition, Professor Schnierle and her co-workers had inserted the gene for the HERV-K envelope protein into the MVA genome. After the inoculation, the gene is read in the cells and the envelope protein is formed. It is presented to the immune system as antigen and an immune response can be induced.

Then the PEI scientists performed investigations to establish whether their "vaccine" could be used both for therapeutic and for prophylactic purposes: For the therapeutic approach, they first injected the genetically modified mouse cancer cells, then waited ten days until lung metastases were formed and then treated part of the mice with the MVA vaccine. The tumours grew considerably more slowly in the vaccinated animals and fewer metastases were observed than in the non-vaccinated animals. However, complete tumour remission was not achieved.

With regard to the prophylactic vaccination, the effect was even more significant: Here, the animals were at first vaccinated twice with the virus (days 0 and 21), and the cancer cells were administered twelve days later. The animals thus vaccinated were protected entirely from tumour development – no metastases could be identified.

"The findings have shown for the first time that the HERV-K envelope protein could be a useful target for the development of a vaccine, and may be able to provide new options for the treatment of various tumours" explained Professor Schnierle.

Original publication

DOI:10.1371/journal.pone.0072756

Kraus B, Fischer K, Büchner SM, Wels W, Löwer R, Sliva K, Schnierle B (2013): Vaccination directed against the human endogenous retrovirus-K envelope protein inhibits tumor growth in a murine model system.
PLoS One 8: e72756.
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