Introduction

New approach to increase the effectiveness of anti-immune checkpoint antibodies with microRNAs that target PD-L1 in lymphomas associated with the Epstein-Barr Virus (EBV). MiRNAs provide an effective way to alter the IC mRNA from within the cell. The invention, based on 3D microfluidic chips, offers a rapid alternative to humanized mice used for human tropic viruses such as EBV, HPV and HIV, to test both tumor immunogenicity and anticancer compounds.

Technical features

Solid tumor immunotherapy is becoming a coveted therapeutic alternative instead of chemotherapy and radiotherapy, but the success of antibodies against immune checkpoints proteins is limited in most tumors (approximately 15-20% of all tumors are caused from infectious agents). Viruses cause over 1.3 million people to get sick with cancer every year around the world. The invention concerns microRNAs together with the use of IC antibodies for the improvement of the overall response rate (ORR) for virus-associated lymphomas but also for other cancers. While antibody-based immunotherapy has been approved for several types of cancer, there are no clear clinical data for EBV-infected tumors even though EBV can alter immune checkpoints. The invention shows how EBV increases PD-L1 and how it is possible to reconstitute the immunogenicity of the tumor by introducing miR-34a into virus-infected lymphomas. A rapid assessment of tumor immunogenicity is critical to designing an appropriate therapy.

Possible Applications

• Therapy for cancers associated with EBV (such as diffuse large B cell lymphoma and Burkitt’s lymphoma);
• Lymphomas in AIDS and transplant patients;
• Nasopharyngeal carcinoma;
• Gastric cancer
• Hodgkin’s lymphoma and other solid tumors.

Advantages

• Better tissue penetration;
• Faster therapeutic response;
• Less toxic approach.