Cancer Immunology, Immunotherapy

, Volume 10, Issue 2–3, pp 157–166 | Cite as

Toxicity studies of liposome-encapsulated immunomodulators administered intravenously to dogs and mice

  • Ian R. Hart
  • William E. Fogler
  • George Poste
  • Isaiah J. Fidler
Original Articles


Multilamellar liposomes containing lymphokines from mitogen-stimulated rat lymphocytes were injected IV into BALB/c or (C57BL/6×C3H)F1 mice and Beagle dogs to evaluate their potential toxicity. Animals received either single or multiple (×3, ×4, or ×6) injections. All animals receiving liposomes remained clinically healthy. No hematologic changes were detected in liposome-treated mice, but lymphocytosis was detected in the treated dogs. Slight elevation of serum alkaline phosphatase and glutamine oxalo-acetic transaminase levels was also found in treated dogs, and occasional animals showed elevated serum bilirubin levels. No histologic evidence of liver damage was found in these animals. No gross or histologic changes were detected in any major organ systems in treated animals. Mononuclear cells isolated from the peripheral blood of dogs that received liposome-encapsulated lymphokines IV were tested for in vitro cytotoxicity against allogeneic tumor cell lines. Lymphocyte-, monocyte-, and natural killer cell-mediated cytotoxicity in vitro was unaltered. Murine alveolar and peritoneal macrophages harvested 24 h after injection of liposome-encapsulated lymphokines exhibited significant tumoricidal activity in vitro, but activation depended on the route of liposome administration. These data indicate that liposome-encapsulated lymphokines do not cause significant toxicity in vivo and are able to activate macrophages in specific anatomic compartments.


Serum Alkaline Phosphatase Serum Bilirubin Level Tumoricidal Activity Hematologic Change Anatomic Compartment 
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Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • Ian R. Hart
    • 1
  • William E. Fogler
    • 1
  • George Poste
    • 2
  • Isaiah J. Fidler
    • 1
  1. 1.Cancer Metastasis and Treatment LaboratoryNCI Frederick Cancer Research CenterFrederick
  2. 2.New York State Department of HealthRoswell Park Memorial InstituteBuffaloUSA

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