Enhanced killing of therapy-induced senescent tumor cells by oncolytic Measles vaccine viruses

  1. Timo Weiland1
  2. Johanna Lampe1
  3. Frank Essmann2
  4. Sascha Venturelli1
  5. Alexander Berger1
  6. Sascha Bossow3
  7. Susanne Berchtold1
  8. Klaus Schulze-Osthoff2
  9. Ulrich M. Lauer1,
  10. Michael Bitzer1,*


Therapy-induced senescence (TIS) as a permanent growth arrest can be induced by various stimuli, including anticancer compounds. TIS has emerged as a promising strategy to overcome resistance phenomena. However, senescent cancer cells might regain proliferation activity in vivo or even secrete tumor-promoting cytokines. Therefore, successful exploitation of TIS in cancer treatment simultaneously requires the development of effective strategies to eliminate senescent cancer cells. Virotherapy aims to selectively hit tumor cells, thus a combination with senescence-inducing drugs was explored. As a model we chose measles vaccine virus (MeV), which does not interfere with cellular senescence by itself. In different tumor cell types, such as hepatoma, pancreatic and mammary gland carcinoma, we demonstrate efficient viral replication and lysis after TIS by gemcitabine, doxorubicin or taxol. Applying real time imaging, we even found an accelerated lysis of senescent cancer cells, supporting an enhanced viral replication with an increase in cell-associated and released infectious MeV particles. In summary, we show as a proof-of-concept that senescent tumor cells can be efficiently exploited as virus host cells by oncolytic MeV. These observations open up a new field for preclinical and clinical research to further investigate TIS and oncolytic viruses as an attractive combinatorial future treatment approach.

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The main focus of ageing research is to prevent/combat age-related disease and disability, allowing everyone to live healthier lives for longer.