Science: increasing collagen affinity can improve cancer immunotherapy

September 1, 2019 / Biovalley BIOON / - -- cancer immunotherapy based on immunocheckpoint inhibitors (CPI) and interleukin-2 (IL-2) is becoming more and more common because of their impressive ability to activate the patient's immune system to fight cancer However, systemic activation of the immune system is not without risk, immunotherapy is usually accompanied by serious adverse events In order to solve this problem, in a new study, researchers from the University of Chicago, Switzerland, Lausanne Institute of technology and Tokyo University in Japan, in view of the leakage of the tumor vascular system, exposed the tumor matrix collagen to the blood components, through coupling (for antibodies) or recombinant fusion (for cytokines) with the blood protein VWF (von Willebrand Factor) the collagen binding domain (CBD) of A3 domain is combined to make the immunocheckpoint inhibitor (CPI) - anti-CTLA4 antibody (α CTLA4) + anti-PD-L1 antibody (α PD-L1) - and cytokine IL-2 target tumors, so as to play a role locally The related research results were recently published in the Journal of Science Translational Medicine, and the title of the paper was "targeted antibody and cytokine cancer immunologies through collagen affinity" Picture from Science Translational Medicine, 2019, DOI: 10.1126/scitranslmed.aau3259 The researchers found that intravenous CBD proteins were mainly accumulated in tumors Cbd-cpi formed by coupling with CBD or cbd-il-2 formed by fusion with CBD reduces the systemic toxicity of α - CTLA4 combination therapy and IL-2, for example, eliminating the hepatotoxicity of immunosuppressant molecules and reducing the pulmonary edema caused by IL-2 Compared with unmodified CPI and IL-2, cbd-cpi and cbd-il-2 inhibited tumor growth, and cbd-cpi and cbd-il-2 increased the number of tumor infiltrating CD8 + T cells In the model of breast cancer in situ, the combination of cbd-cpi and cbd-il-2 eradicated tumors in 9 out of 13 animals, while the combination of unmodified CPI and IL-2 eradicated tumors in only 1 animal Therefore, the A3 domain of vWF can be used to improve the safety and efficacy of systemic cancer drugs with high transformation potential (BIOON Com) reference: Jun Ishihara et al Targeted immunity and cytokine cancer immunity through collagen affinity Science Translational Medicine, 2019, DOI: 10.1126/scitranslmed.aau3259