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Localized immunotherapy new possibility to treat bladder cancer

December 08, 2016

Antibody-based immunotherapy is a new promising method to treat cancer. Unfortunately, today's treatments can result in adverse side effects. New findings from Uppsala University show an alternative way to administer the therapy, which has the same effect on the tumour but less impact other parts of the body.

In antibody-based immunotherapy drugs are used to stimulate the body's own immune cells to attack and destroy the tumour cells. This method is presently used to treat certain types of metastasised cancer, such as melanoma and bladder cancer. However, a disadvantage of the therapy is that the drug is injected in the blood, which will lead to an exposure of the whole body and thereby possible adverse events.

An alternative strategy would be to administer the drug directly in or close to the tumour, provided that this still leads to the desired immune cell stimulation. In the present study a group of researchers, led by Sara Mangsbo at Department of Immunology, Genetics and Pathology, IGP, has demonstrated that a local immune activation in the tumour area had the same tumour inhibiting capacity as when the drug was delivered in the blood.

'We found that the therapy that we tested in a model system of bladder cancer could stimulate the immune cells to find and attack the cancer cells, even if it was administered locally. These results are very promising since they indicate that it's not necessary to activate the body's whole immune system, but only the one that is relevant in the tumour. This way adverse events caused by the drug can be reduced,' says Sara Mangsbo.

In the study immune activation was achieved by administering blocking antibodies close to the tumour. The results complement the researcher's previous findings where they found that a direct immune stimulatory antibody had superior anti-tumour capacity when used locally at the tumour, as compared to after injection into the blood.

The hope is also that the immune cells, not the drug itself, can find potential metastases and eliminate them. To understand if and how this is happening, further research is required. The present results are based on studies in mice and to determine if drug administration to the tumour results in fewer adverse events in patients, as compared to injections into the blood stream, clinical studies are also needed.
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The study is a collaboration with researchers in Lund and in Canada and was recently published in European Journal of Immunology.

Luuk van Hooren et al, Local checkpoint inhibition of CTLA-4 as a monotherapy or in combination with anti-PD1 prevents the growth of murine bladder cancer, European Journal of Immunology november 2016, http://onlinelibrary.wiley.com/doi/10.1002/eji.201646583/abstract

More information:

Sara Mangsbo, associated Professor and researcher at Department of Immunology, Genetics and Pathology (IGP), Uppsala university, sara.mangsbo@igp.uu.se, tel 070-425 08 78

Uppsala University

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