Potential use of bacteria in cancer immunotherapy

12 Feb 2008
A strain of bacteria able to stimulate only a systemic immune response has been identified by a group at the European Institute of Oncology in Milan (IEO). The study, published in Immunity, may have significant relevance for the use of bacteria in cancer treatment.

A group of researchers from the Department of Experimental Oncology at the IEO has previously described a novel therapeutic approach to destroy infected melanoma cells through the administration of an a-virulent strain of Salmonella typhimurium.

After oral administration, the same strain of bacteria is injected directly into the tumour. The T-cells attack and kill the tumour cells which have in the mean time become infected.

However, repeated oral administrations were not feasible due to an inhibitory effect of the local mucosal immune response. Dr Rescigno, head of the Immunotherapy group stated: “When the bacteria are given orally an undesired local response is also induced resulting in antibody production within the blood and intestine, blocking the entry of any more bacteria. We were interested to understand the mechanism controlling the immune response to different bacterial strains, in order to improve our vaccine.”

Having done this, they went on to show that the local response, unwanted in the case of an anti-cancer vaccine, takes place in thickenings of the epithelium of the small intestine known as Peyer’s Patches. Thereafter they were able to identify a strain of non-invasive Salmonella typhimurium which is unable to reach the Peyer’s Patches, and consequently will not invoke a local response.

“This strain does not induce the production of antibodies locally and can therefore be re-injected when required, even after several years, to re-activate the T-cell response against the infected tumour cells” explained Rescigno.

This strain could have a further application in the generation of recombinant bacteria expressing a tumour-specific antigen in order to activate a tumour-specific response; as the T-cells activated by oral administration will attack not only the infected cells but also those which display the tumour antigen on their surface.

The advantage being that this strain could be indefinitely administered to the patient without the risk of developing a local response that would prevent bacterial entrance in subsequent vaccinations.