Starvation-Induced Differential Virotherapy Using an Oncolytic Measles Vaccine Virus

• Main Authors: Gabriel Scheubeck, Susanne Berchtold, Irina Smirnow, Andrea Schenk, Julia Beil, Ulrich M. Lauer
• Format: Article
• Language: English
• Published: MDPI AG 2019-07-01
• Series: Viruses
• Subjects: starvation; fasting; virotherapy; oncolysis; measles vaccine virus
• Online Access: https://www.mdpi.com/1999-4915/11/7/614

Starvation sensitizes tumor cells to chemotherapy while protecting normal cells at the same time, a phenomenon defined as differential stress resistance. In this study, we analyzed if starvation would also increase the oncolytic potential of an oncolytic measles vaccine virus (MeV-GFP) while protecting normal cells against off-target lysis. Human colorectal carcinoma (CRC) cell lines as well as human normal colon cell lines were subjected to various starvation regimes and infected with MeV-GFP. The applied fasting regimes were either short-term (24 h pre-infection) or long-term (24 h pre- plus 96 h post-infection). Cell-killing features of (i) virotherapy, (ii) starvation, as well as (iii) the combination of both were analyzed by cell viability assays and virus growth curves. Remarkably, while long-term low-serum, standard glucose starvation potentiated the efficacy of MeV-mediated cell killing in CRC cells, it was found to be decreased in normal colon cells. Interestingly, viral replication of MeV-GFP in CRC cells was decreased in long-term-starved cells and increased after short-term low-glucose, low-serum starvation. In conclusion, starvation-based virotherapy has the potential to differentially enhance MeV-mediated oncolysis in the context of CRC cancer patients while protecting normal colon cells from unwanted off-target effects.