New approach to cancer immunotherapy 'universally applicable'

Updated

Tricking the immune system into viewing cancer as an invading virus could lead scientists to the holy grail of a universal tumour vaccine, research suggests.

A first step towards the revolutionary new therapy has already been taken by researchers who tested it on three patients with melanoma, the deadliest form of skin cancer.

In each case, strong immune responses against the cancer were seen, although the early stage trial was not designed to measure the treatment's effectiveness.

The approach involves taking the genetic instructions for a specific cancer protein, encoded in a molecule of RNA, and using it to stimulate the immune system.

The RNA triggers the kind of immune response normally employed to see off viruses - only in this case, the targets are cancer cells.

The German research raises the possibility of a vaccine that can be tailored for any kind of cancer, or even new versions of a disease that evolve as it progresses within the same patient.

Writing in the journal Nature, the scientists led by Professor Ugur Sahin, from Johannes Gutenberg University in Mainz, Germany, concluded: "Virtually any tumour antigen (protein) can be encoded by RNA. Thus, the nanoparticulate RNA immunotherapy approach introduced here may be regarded as a universally applicable novel vaccine class for cancer immunotherapy."

RNA is a molecular cousin of DNA and used to transfer genetic code instructions to protein-making machinery in cells.

To make their vaccine, the scientists created artificial nanoparticle "cells" consisting of RNA surrounded by a fatty lipid membrane.

Various RNA sequences were used, representing a range of different cancer proteins, in experiments both involving mice and human patients.

Injected into the bloodstream, the RNA-lipoplex nanoparticles activated immune system dendritic cells in the lymph nodes and spleen.

Dendritic cells "flag up" target proteins to immune system T-cells, thereby priming them to recognise and attack anything else carrying the same molecules. In this way, T-cells were turned against cancer tumours.

Powerful anti-cancer immune responses were seen in the melanoma patients involving both "helper" T-cells which play a role in the production of antibodies, and "killer" T-cells that actively destroy invaders.

Cancer vaccines hold out great promise but are difficult to develop for a variety of reasons. One obstacle is that the immune system is designed to avoid causing collateral damage to the body wherever possible. Often cancer cells look too much like normal cells, and are therefore left alone or attacked only weakly.

Many cancers that have co-evolved with the immune system have developed ways of shielding themselves from it. New immunotherapy drugs now being made available to patients are designed to take the brakes off the immune system so that cancer cannot escape. However, they can have unwanted side effects.

Commenting on the new research in Nature, cancer experts Professor Jolanda de Vries and Professor Carl Figdor, from Radboud University in the Netherlands, wrote: "This nanomedicine platform may give a strong boost to the vaccine field, and the results of forthcoming clinical studies will be of great interest."

Professor Alan Melcher, from the Institute of Cancer Research, said: "Although the research is very interesting, it is still some way away from being of proven benefit to patients."

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