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Preclinical SC and IV repeat-dose toxicology of a cowpea mosaic virus - A cancer immunotherapy candidate

  1. Author:
    Stern,Stephan
    Affonso de Oliveira, Jessica Fernanda
    Gatus, Jamie
    Edmondson,Elijah
    Dobrovolskaia,Marina
    Steinmetz, Nicole F
    Neun, Barry W

  2. Author Address

    Nanotechnology Characterization Lab, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, MD 21702, USA., Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego, 9500 Gilman Dr., La Jolla, La Jolla, CA 92093, USA., Shu and K.C. Chien and Peter Farrell Collaboratory, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA., Center for Nano-ImmunoEngineering, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA., Molecular Histopathology Laboratory, Laboratory of Animal Sciences Program, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, 8560 Progress Drive, Frederick, MD 21701, USA., Department of Bioengineering, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA., Department of Radiology, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA., Institute for Materials Discovery and Design, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA., Moores Cancer Center, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA., Center for Engineering in Cancer, Institute of Engineering Medicine, University of California San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA.,
    1. Year: 2025
    2. Date: Jun
    3. Epub Date: 2025 04 07
  2. Journal: Toxicology Reports
    1. 14
    2. Pages: 102022
  4. Type of Article: Article
  5. Article Number: 102022
  1. Abstract:

    Cancer immunotherapies focus on boosting the immune system to recognize and eliminate tumor cells. Amongst the various biologics under development for cancer immunotherapy, our team has focused on the study of plant viruses in this context. We have shown that intratumoral administration of cowpea mosaic virus (CPMV) relieves the immunosuppressive tumor microenvironment and elicits a potent, systemic and durable anti-tumor immune response. The potency of CPMV has been demonstrated in several tumor mouse models and in companion canine cancer patients. Toward clinical development, we here studied the pharmacology and safety of CPMV. The repeat-dose toxicity of CPMV was evaluated in female Sprague Dawley rats. Rats received three weekly treatments (subcutaneous or intravenous) of a fixed dose (~20 mg/kg), and complete necropsy was performed either 24 hrs (acute toxicity group) or 14 day (recovery group) post-dose. All animals reached the scheduled euthanasia times, and no clinical abnormalities were noted during the study period. Important clinical chemistry, hematology and histopathology findings included decreased albumin/globulin ratio, leukocytosis, neutrophilia, monocytosis, and lymphoid hyperplasia (Dunnett's test, p< 0.05) - these changes support the immunostimulatory mode of action for CPMV. All other changes were considered mild, within historical range for the model, and/or not biologically significant. Neither a maximum tolerated dose (MTD) nor a no-observable adverse effect level (NOAEL) was established in this study. Overall, data indicate a good safety profile for the CPMV cancer immunotherapy candidate. © 2025 The Authors.

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External Sources

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  2. DOI: 10.1016/j.toxrep.2025.102022
  3. PMID: 40276251
  4. PMCID: PMC12019203
  5. PII : S2214-7500(25)00140-4

Library Notes

  1. Fiscal Year: FY2024-2025
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