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Adenovirus-Mediated Inducible Expression of a PD-L1 Blocking Antibody in Combination with Macrophage Depletion Improves Survival in a Mouse Model of Peritoneal Carcinomatosis by Maria Buñuales; Maria Cristina Ballesteros-Briones; Manuela Gonzalez-Aparicio; Sandra Hervas-Stubbs; Eva Martisova; Uxua Mancheño; Ana Ricobaraza; Sara Lumbreras; Cristian Smerdou; Ruben Hernandez-Alcoceba is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.
What is Adenovirus-Mediated Inducible Expression of a PD-L1 Blocking Antibody in Combination with Macrophage Depletion Improves Survival in a Mouse Model of Peritoneal Carcinomatosis about?
Immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in a growing number of malignancies. However, overcoming primary or secondary resistances is difficult due to pharmacokinetics issues and side effects associated with high systemic exposure. Local or regional expression of monoclonal antibodies (mAbs) using gene therapy vectors can alleviate this problem. In this work, we describe a high-capacity adenoviral vector (HCA-EFZP-aPDL1) equipped with a mifepristone-inducible system for the controlled expression of an anti-programmed death ligand 1 (PD-L1) blocking antibody. The vector was tested in an immune-competent mouse model of colorectal cancer based on implantation of MC38 cells. A single local administration of HCA-EFZP-aPDL1 in subcutaneous lesions led to a significant reduction in tumor growth with minimal release of the antibody in the circulation. When the vector was tested in a more stringent setting (rapidly progressing peritoneal carcinomatosis), the antitumor effect was marginal even in combination with other immune-stimulatory agents such as polyinosinic-polycytidylic acid (pI:C), blocking mAbs for T cell immunoglobulin, mucin-domain containing-3 (
Who reads Adenovirus-Mediated Inducible Expression of a PD-L1 Blocking Antibody in Combination with Macrophage Depletion Improves Survival in a Mouse Model of Peritoneal Carcinomatosis?
It is typically read by researchers, students, and practitioners in Biochemistry, Genetics and Molecular Biology.
- Author
- Maria Buñuales; Maria Cristina Ballesteros-Briones; Manuela Gonzalez-Aparicio; Sandra Hervas-Stubbs; Eva Martisova; Uxua Mancheño; Ana Ricobaraza; Sara Lumbreras; Cristian Smerdou; Ruben Hernandez-Alcoceba
- Publisher
- MDPI AG
- Published
- 2021
- Language
- EN
- Field
- Biochemistry, Genetics and Molecular Biology (Life Sciences)