Dual therapy
Combination of immunotherapy and cancer vaccine helped mice with melanoma
Anastasia Kuznetsova-Fantoni, N+1
British scientists have tested a combined cancer treatment on mice with implanted melanoma. The method consists in the simultaneous use of a vaccine that triggers an immune response against tumor cell antigens, as well as a PD-1 checkpoint inhibitor that prevents the tumor from escaping recognition by T-lymphocytes. After 40 days of treatment, the tumor volume in mice treated with combination therapy turned out to be two times smaller than in mice treated only with a PD-1 inhibitor. The study was published in the Journal for Immunotherapy of Cancer (McAuliffe et al., Heterologous prime-boost vaccination targeting MAGE-type antigens promotes tumor T-cell infiltration and improves checkpoint blockade therapy).
One of the methods of treating malignant tumors is immunotherapy, in which doctors stimulate the immune system so that it fights tumor cells itself. This can be done with the help of vaccines that "train" T-lymphocytes to recognize cancer cells and bind to them. Such vaccines carry information about surface proteins that are located on most types of tumors, but are not found on normal cells of the body.
Another common type of cancer immunotherapy is the blockade of immune checkpoints, which prevents tumor cells from leaving T-lymphocytes. This situation occurs in some cases when cancer cells bind to T-lymphocyte receptors and turn off their response, becoming "invisible" to the immune system. PD-1 and PD-L1 inhibitors block these receptors, and cancer cells are again normally recognized by T-lymphocytes.
Researchers led by Benoit J Van den Eynde from Oxford University have created a drug that combines a cancer vaccine with immunotherapy. To do this, they used the adenovirus vector ChAdOx1, which is contained in the coronavirus vaccine from AstraZeneca. Scientists chose this vector because vaccines based on it trigger a strong T-cell response. The viral vector encodes the MAGE and NY-ESO-1 proteins located on the surface of cancer cells. These antigens learn to recognize T-lymphocytes. In addition, the researchers decided to enhance the effect of the vaccine and additionally introduce a PD-1 inhibitor, which prevents tumor cells from avoiding recognition by T-lymphocytes.
The combined treatment was tested in experiments on mice implanted with melanoma cells subcutaneously. The animals were divided into two groups of 6 mice: one was treated only with a PD-1 inhibitor, and the second was also vaccinated with three doses of the developed drug at intervals of two weeks.
40 days after the start of treatment, the tumor volume in mice from the combination therapy group was two times smaller than in animals treated only with a PD-1 inhibitor (p<0.0001). In the group that received combination therapy, three mice survived until the end of the experiment (50 days), and in the group that was administered only a PD-1 inhibitor, one mouse survived (p<0.001).
At the end of this year, doctors plan to begin clinical trials of the joint use of a cancer vaccine and immune checkpoint inhibitors in 80 people with lung cancer.
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