Immune checkpoint inhibitors augment the anti-tumor effect of liposomal chemotherapy
Jennifer Solgaard Jørgensena, Fredrik Melandera, Rasmus Eliasena, Anders Elias Hansena, Andreas Kjærb, Thomas Lars Andresena aColloids and Biological Interface Group. Dept. of Micro- and Nanotechnology. Technical University of Denmark. Produktionstorvet, Building 423, 2800 Kgs. Lyngby, Denmark; bDept. of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Dept. of Biomedical Sciences, Rigshospitalet and University of Copenhagen. Blegdamsvej 3B, Building 12.3, 2200 København N, Denmark
During the last decades the possible treatments methods for cancer have changed considerably and the tumor microenvironment appears to be the cornerstone of new therapies, including immunotherapy. Cancer immunotherapy aims at re-establishing or improving the ability of the immune system to fight cancer. One example of immunotherapy is immune checkpoint inhibitors which have been shown to induce tumor regression and improve overall survival in selected cancer patients, and many studies are combining the checkpoint inhibitors with chemotherapy with great effect. Here, we present data on liposomal chemotherapy combined with the immune checkpoint inhibitor anti-programmed death 1 (PD-1) to augment the anti-tumor effect of the chemotherapy. The liposomes contain the chemotherapeutic oxaliplatin and are designed to improve the anti-tumor effect of oxaliplatin. Firstly, by using flow cytometry we found that neither free oxaliplatin nor liposomal oxaliplatin influenced the expression levels of PD-1 on cytotoxic T-cells in the tumor microenvironment of colorectal CT26 tumors. Next, we examined the efficacy of the combination treatment and our data showed that adding anti-PD-1 to the liposomal chemotherapy regimen enhanced the anti-tumor effect of the chemotherapy and led to improved survival in mice bearing CT26 colorectal tumors.
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