Enhanced Anti-Tumor Effect of Double E1B 19 kDa- and E1B 55 kDa-Deleted Oncolytic Adenovirus in Combination with Radiotherapy

Recent research from Seoul, Korea, has led to the development of a double E1B 19 kDa- and E1B 55 kDa-deleted oncolytic adenovirus (Ad-DeltaE1B19/55) that, in combination with radiotherapy, shows a significantly enhanced anti-tumor effect. This new therapy triggers tumor cell apoptotic pathways, leading to increased cytotoxicity and higher levels of key proteins involved in cell death. The study, published in Gene Therapy, demonstrated that the combination of Ad-DeltaE1B19/55 and radiation was more efficacious than the combination of Ad-DeltaE1B55 and radiation.

Key Takeaways:

  • The double E1B 19 kDa- and E1B 55 kDa-deleted oncolytic adenovirus (Ad-DeltaE1B19/55) showed greater cytotoxicity than the single E1B 55 kDa-deleted oncolytic adenovirus (Ad-DeltaE1B55) when combined with radiotherapy.
  • Tumors treated with Ad-DeltaE1B19/55 and radiation showed large areas of necrosis and apoptosis, with the corresponding induction of p53.
  • The combination of Ad-DeltaE1B19/55 and radiation was more efficacious than the combination of Ad-DeltaE1B55 and radiation.
  • Higher levels of key proteins involved in cell death, such as p53, phospho-p53, phospho-Chk1, phospho-Chk2, PI3K, phospho-AKT, cytochrome c, and cleavage of PARP and caspase-3, were observed in cells treated with Ad-DeltaE1B19/55 compared with those treated with Ad-DeltaE1B55.
  • The study's findings provide a strong therapeutic rationale for combining radiation therapy with E1B 19 kDa-deleted oncolytic Ad.

Statistics:

  • The combination of Ad-DeltaE1B19/55 and radiation showed a significant therapeutic benefit, with tumors treated with Ad-DeltaE1B19/55 and radiation showing large areas of necrosis and apoptosis.
  • The study involved a comparison of the efficacy of Ad-DeltaE1B19/55 and Ad-DeltaE1B55 when combined with radiation therapy.
  • The researchers observed higher levels of key proteins involved in cell death, including p53, phospho-p53, phospho-Chk1, phospho-Chk2, PI3K, phospho-AKT, cytochrome c, and cleavage of PARP and caspase-3, in cells treated with Ad-DeltaE1B19/55 compared with those treated with Ad-DeltaE1B55.

Sources:

  • Kim, J., et al. (2009). Double E1B 19 kDa- and E1B 55 kDa-deleted oncolytic adenovirus in combination with radiotherapy elicits an enhanced anti-tumor effect. Gene Therapy, 16(9), 1111-1121.
  • Yonsei University, Institute for Cancer Research. Contact J. Kim, Brain Korea 21 Project for Medical Sciences, Institute for Cancer Research, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
  • Nature Publishing Group, 345 Park Avenue South, New York, NY 10010-1707, USA.