A combination of anti-angiogenic antibodies and immunotherapy has shown effectiveness against solid tumours in a mouse study, researchers have reported.
Dr Abhishek Kashyap and colleagues at the University of Basel, Switzerland set out to investigate combinations of treatments to improve the effectiveness of CD40-based immunotherapy.
CD40 antibodies activate the CD40 receptor on the surface of immune cells and stimulate the production of killer T-cells. Whilst the therapy had shown promise in pre-clinical studies, it has proven less effective in clinical trials than hoped.
Researchers had noticed that CD40 antibodies only lead to an increase in killer T-cells in peripheral areas of the tumour, and not inside the mass. Kashyap and colleagues thought that this could be due to the nature of blood vessels inside tumours.
Dr Kashyap explains: “Normally, the blood vessels of a tumour are leaky or stunted. Therefore, there is no good way for killer T-cells to get inside. Our hypothesis was that the killer cells are able to invade the tumour and destroy it only if there are enough healthy blood vessels.”
So, the team added two other antibodies that boost the growth of healthy blood vessels. One was bevacizumab, also known as Avastin, which targets VEGFA. The other is an antibody still in development which blocks angiopoietin-2.
In tests on mouse models of colorectal, breast and skin cancer, they found that the combination leads to “a more effective destruction of tumours” than the anti-CD40 antibody alone. Details appeared recently in the journal PNAS.
Dr Kashyap believes that adds that patients who do not respond to current immunotherapy options could benefit most from this new treatment. “Our results illustrate how important it is to understand the biology of tumours,” Dr Kashyap concludes.
Several early clinical trials of similar therapies are already under way in cancer patients.
Kashyap AS, Schmittnaegel M, Rigamonti N, Pais-Ferreira D, Mueller P, Buchi M, Ooi CH, Kreuzaler M, Hirschmann P, Guichard A, Rieder N, Bill R, Herting F, Kienast Y, Dirnhofer S, Klein C, Hoves S, Ries CH, Corse E, De Palma M, Zippelius A (2019) “Optimized anti-angiogenic reprogramming of the tumor microenvironment potentiates CD40 immunotherapy”, PNAS, doi: 10.1073/pnas.1902145116