Robust oncolytic virotherapy induces tumor lysis syndrome and associated toxicities in the MPC-11 plasmacytoma model

Lianwen Zhang, Michael B. Steele, Nathan Jenks, Jacquelyn Grell, Marshall Behrens, Rebecca Nace, Shruthi Naik, Mark J Federspiel, Stephen J Russell, Kah-Whye Peng

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Tumor-selective oncolytic vesicular stomatitis viruses (VSVs) are being evaluated in clinical trials. Here, we report that the MPC-11 murine plasmacytoma model is so extraordinarily susceptible to oncolytic VSVs that a low dose of virus leads to extensive intratumoral viral replication, sustained viremia, intravascular coagulation, and a rapidly fatal tumor lysis syndrome (TLS). Rapid softening, shrinkage and hemorrhagic necrosis of flank tumors was noted within 1-2 days after virus administration, leading to hyperkalemia, hyperphosphatemia, hypocalcemia, hyperuricemia, increase in plasma cell free DNA, lymphopenia, consumptive coagulopathy, increase in fibrinogen degradation products, decreased liver function tests, dehydration, weight loss, and euthanasia or death after 5-8 days. Secondary viremia was observed but viral replication in normal host tissues was not detected. Toxicity could be mitigated by using VSVs with slowed replication kinetics, and was less marked in animals with smaller flank tumors. The MPC-11 tumor represents an interesting model to further study the complex interplay of robust intratumoral viral replication, tumor lysis, and associated toxicities in cases where tumors are highly responsive to oncolytic virotherapy.

Original languageEnglish (US)
Pages (from-to)2109-2117
Number of pages9
JournalMolecular Therapy
Volume24
Issue number12
DOIs
StatePublished - Dec 1 2016

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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