The synergistic effect of the combination of anti-angiogenesis drugs and cancer immunotherapy has been proven again!

Recently, a study conducted by scientists from the University of Basel and Roche in animal models has proved the synergistic effect of anti angioproliferative drugs combined with cancer immunotherapy The combination of this therapy is Roche's anti-CD40 antibody, Avastin, and an anti angiopoietin 2 (Ang2 / angpt2) antibody The study was published in the proceedings of the National Academy of Sciences (PNAs) CD40, a receptor on the surface of immune cells, has long been a hot topic in oncology because activation of CD40 stimulates T cells that kill cancer cells Previously, it has shown good results in preclinical studies However, in the subsequent clinical trials, the therapeutic effect of CD40 antibody is far lower than the researchers' expectation, and only less than 20% of patients receive CD40 antibody to alleviate the disease How to improve the efficacy of CD40 antibody is a problem that researchers have been pursuing The cancer immunology research team of Basel University found that although anti-CD40 antibody can significantly increase the number of CD8 positive T cells that kill tumors, these T cells only stay at the edge of the tumor, and can not enter the tumor The researchers suspect that this is due to leakage or hypoplasia of the blood vessels that dominate the tumor Dr Abhishek Kashyap, the lead author of the study, said: "our hypothesis is that the effector cells can infiltrate and destroy tumors if there are enough healthy blood vessels there "So they worked with scientists at Roche innovation center to combine anti-CD40 antibodies with two anti angiogenic antibodies in an attempt to stabilize the structure of tumor blood vessels They are Avastin and anti angiogenic antibodies targeting Ang2 The researchers tested the new antibody combination in mice with different types of cancer, including colorectal, breast and skin cancer The results showed that these two antiangiogenic drugs increased the number of complete blood vessels in tumor, and then increased the number of effective T cells attacking cancer Moreover, this antibody combination can promote the occurrence of inflammatory reaction in tumor microenvironment Blocking Ang2 can also stimulate the infiltration and redistribution of CD8 positive T cells in tumor These synergistic effects make the triple therapy significantly delay the proliferation of tumor and prolong the life of animals in the mouse model "Our experimental results show that it is very important to understand the biology of tumor "Dr Kashyap said He believes that patients with "cold" tumors benefit most from this innovative mix "Anti angiogenic antibodies can make 'cold' tumors' hot ', which makes immunotherapy more effective."