Prediction of systemic cytokine exposure in human after IV administration of oncolytic myxoma virus, using quantitative systems pharmacology modeling

Collaboration with OncoMyx Therapeutics - Presented at the American Association for Cancer Research, Annual Meeting 2021

Abstract

  • Oncolytic viruses selectively replicate in and lyse tumor cells and provide stimulation to the immune system. The genome of MYXV is relatively large and is amenable to engineering for expression of transgenic proteins.
  • Myxoma can infect leukocytes in the peripheral blood and initiate early gene transcription, but not late gene transcription nor replication in peripheral blood leukocytes.
  • A quantitative systems pharmacology (QSP) model of oncolytic immunotherapies based on the myxoma virus (MYXV) platform was constructed to:
    • Predict systemic cytokine exposure from transgene expression and secondary response
    • Determine safe doses based on comparisons of projected cytokine levels to previously established cytokine exposure at maximum tolerated doses of IV administered cytokines

 

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