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A New Therapeutic Strategy for Cancer

Cancer cells are very good at eluding our immune system. In fact, a wide range of studies have highlighted the ability of tumours to block our defence systems by producing proteins (i.e., PD-L1) that are capable of blocking the activity of immune cells like our T-lymphocytes. 

In this context, the research project coordinated by Sapienza Professor Pankaj Trivedi, in collaboration with the Beth Israel Deaconess Medical Centre (BIDMC) of the Harvard Medical School, opens a new therapeutic approach to the treatment of tumours caused by infections. The results point to how two combined actions can be applied to neutralise the immunoevasion mechanism. The strategy behind this new therapy exploits the antibodies that keep T-lymphocytes at bay, while, at the same time, inserting small RNA molecules in the tumour cells so they stop producing the protein that blocks the antibodies. The results of the study have been published on Leukemia.

Considering that ca. 15% of all human tumours originate from infections, the research team identified the immunoevasion mechanism of the Epstein-Barr Virus (EBV), associated with Burkitt’s Lyphoma, the lymphoma that attacks large B cells, Hodgkin’s Lymphoma and nasopharyngeal cancer.

The direct observation of the interaction between immune system T-Cells and tumoral cells was made possible by a micro-fluidic 3D chip, an innovative method developed by Sapienza graduate Eleni Anastasiadou, who currently conducts research at Harvard University and is the first author of the study. Harvard Medical School and Sapienza University have a joint patent for combinatorial immunotherapy of EBV associated cancers.

Thanks to this innovative method, the researchers were able to describe the behaviour of the virus and its molecular processes. “A range of very aggressive tumours,” explains Professor Pankaj Trivedi from the Sapienza Department of Experimental Medicine, “produce the PD-L1 molecule on the surface of their cells, which, bonding with the T-lymphocyte receptors, PD-1s, disactivates them and fools our immune systems.”

This study further widens the scenario for immunotherapy, which, to date, is based on the use of monoclonal antibodies, but only has a success rate in 20 to 40% of cases. “Our hope is that the combination of antibodies directed against PD-L1 and RNA molecules,” concludes Professor Trivedi, “will have a greater efficacy than traditional therapies and significantly boost success cases.”



Epstein−Barr Virus-encoded EBNA2 Alters Immune Checkpoint PD-L1 Expression by Downregulating miR-34a in B-cell Lymphomas - Eleni Anastasiadou, Dina Stroopinsky, Stella Alimperti, Alan L Jiao, Athalia R Pyzer, Claudia Cippitelli, Giuseppina Pepe, Martina Severa, Jacalyn Rosenblatt, Marilena P Etna, Simone Rieger, Bettina Kempkes, Eliana M Coccia, Shannan J Ho Sui, Christopher S Chen, Stefania Uccini, David Avigan, Alberto Faggioni, Pankaj Trivedi & Frank J Slack - Leukemia Published: 26 June 2018 DOI:  10.1038/s41375-018-0178-x

For further information:

Pankaj Trivedi, Department of Experimental Medicine, Sapienza University