PNAs: combination of three antibodies can significantly improve cancer immunotherapy

January 9, 2020 / Biovalley BIOON / - -- in a new study, researchers from the University of Basel, Switzerland, found that the simultaneous use of antibodies with two different mechanisms of action can more effectively destroy tumors The relevant research results were recently published in PNAS, and the title of the paper was "optimized antigenic reprogramming of the tumor microenvironment potents CD40 immunotherapy" Patients who are unresponsive to current cancer immunotherapy may benefit the most from this new treatment Picture from PNAs, 2019, DOI: 10.1073/pnas.1902145116 In recent years, cancer immunotherapy has aroused great hope These new treatments can recruit the body's immune system to destroy cancerous tissue In preclinical studies, the activation of CD40 receptors on the surface of immune cells to stimulate antibodies produced by natural killer T cells has shown encouraging effects However, in subsequent clinical trials, the success of anti-CD40 antibody was far less than expected - less than 20% of patients responded Now, in this new study, these researchers have shown in animal models that by combining anti-CD40 antibodies with two other antibodies attached to tumor blood vessels, the effect of anti-CD40 antibodies can be significantly improved The starting point of the new study, which opens the way to cancer, is to observe that the delivery of anti-CD40 antibody will lead to the increase of killer T cells as expected, but these killer T cells can only be detected in the peripheral area of the tumor rather than in the inside of the tumor The researchers suspect this is due to the nature of the tumor's blood vessels Dr Abhishek Kashyap, the first author of the paper, said, "in general, tumors have vascular leakage or hypoplasia As a result, killer T cells cannot enter it Our hypothesis is that these killer T cells can invade the tumor and destroy it only if there are enough healthy blood vessels " So the researchers used anti-CD40 antibodies in combination with two other anti angiogenic antibodies that stabilize tumor blood vessels One of them, Avastin, has been approved for cancer treatment, while the other is still in clinical development The researchers then tested the new combination of antibodies against different types of cancer, such as colorectal, breast and skin cancer, in several animal models As expected, the combination of these three antibodies significantly improved tumor tissue destruction in all cancers More detailed analysis also shows that this success is based on a predictive mechanism: the addition of two anti angiogenic antibodies ensures that the tumor has more complete blood vessels However, surprisingly, this new study also shows that this combination of antibodies can enhance the immune system in many ways, such as better infiltration of killer T cells into tumors, and promote the occurrence of inflammatory reactions against tumors in tumor microenvironment "Our results illustrate the importance of understanding tumor biology," Kashyap said He thinks patients with cold tumours - tumors that don't respond well to immunotherapy - can benefit the most from this new combination "These two anti angiogenic antibodies may turn a cold tumor into a hot one, which makes immunotherapy work better." At the same time, early clinical trials of several similar therapies in humans are under way (BIOON Com) reference: 1 Abhishek s Kashyap et al Optimized antigiogenic reprogramming of the more microenvironment potents CD40 immunotherapy PNAs, 2019, doi:10.1073/pnas.1902145116 2.Novel combination of antibodies leads to significant improvement in cancer immunotherapy https://medicalxpress.com/news/2019-12-combination-antibodies-significant-cancer-immunotherapy.html