Identifying the enemy within

A potential anti-cancer therapy
Sep 22nd 2009
From Economist.com

An implant that instructs the immune system to fight cancer

How do you do, granulocyte-macrophage colony-stimulating factor? CANCER is deadly because it comes from within and evades the body’s natural defences. Attempts to train the immune system to recognise and attack cancers have so far failed. But a new technique that uses doped implants is showing promise.

The implants in question are tiny biodegradable discs, just millimetres across, that are impregnated with a substance called granulocyte-macrophage colony-stimulating factor which attracts dendritic cells, the main orchestrators of immune responses. Dendritic cells normally latch on to bacteria and viruses before migrating to the lymph nodes, where they present the alien material to the immune system’s “killer” T-cells that seek and destroy such invaders. But dendritic cells do not normally recognise cancer cells as dangerous.

Omar Ali and his colleagues at Harvard University have found a way to teach the dendritic cells to identify cancer. They do this by taking molecules from a biopsy of a patient’s tumour and attaching them to the implant, along with a substance called cytosine-guanosine oligonucleotide that dendritic cells recognise as being associated with infection. Attracted by the granulocyte-macrophage colony-stimulating factor, the dendritic cells are temporarily captured by pores in the spongy implant and exposed to the chemical cocktail that prompts them to take the cancer cells to the T-cells so that they can be destroyed.

The Harvard team has tested its system on mice with skin cancer. All of the murines with melanoma that had not received an implant died within 25 days; 90% of those with implants survived. The study was published in Nature Materials earlier this year.

The group has now repeated the experiments in mice with gliomas, which are tumours that start in the brain or spine. Although the results are not due to be published until later this year, Dr Ali describes them as “very encouraging” and similar to those achieved in melanomas. He adds that experiments on the use of the implants in mice with breast cancers have been positive, although those with lung cancer were not. Early experiments also suggest that the discs are effective even against some late-stage forms of cancer in mice. Clinical trials of the implants in human patients with late-stage skin cancer are due to begin in June 2010.

America’s Food and Drug Administration has already approved both the polymer the implant is made from and the active agents it uses. Although approval for the implants will still be required, the process could be relatively quick. David Mooney, one of Dr Ali’s colleagues, has established a spin-off biotech company called InCytu to commercialise the technology.

Dr Mooney, who has previously worked on implants to stimulate blood-vessel growth and bone regeneration, says such a device could also be used to reduce immune responses, as well as boosting them. He has started tests on animals to investigate whether the implants could be used to combat chronic inflammatory diseases and autoimmune diseases, such as arthritis and diabetes.

Comment

This theory has been around for a while, and is only now coming to fruition. The main benefit is that healthy cells are not attacked, and there are little or no side effects since small doses are given. A biopsy of the tumor is done to get an impression of what the tumor looks and acts like. Since the individuals own immune system is the one doing the work there is no outside alien particles to react to.