Immunotherapy with keyhole limpet hemocyanin: efficacy and safety in the MB-49 intravesical murine bladder tumor model

J Urol. 1994 Jun;151(6):1718-22. doi: 10.1016/s0022-5347(17)35352-1.

Abstract

The antitumor activity and potential toxicity of a clinical-grade keyhole limpet hemocyanin preparation (KLH-Immune Activator; KLH-IA) were determined in the MB-49 intravesical murine bladder tumor model. Mice were immunized subcutaneously with KLH-IA two weeks prior to intravesical implantation of MB-49 tumor cells. Treatment consisted of intravesical KLH-IA (10 or 100 micrograms.) 1, 4, 7, 14 and 21 days after implantation. Control animals either were not immunized prior to tumor implantation and KLH-IA treatment, or were immunized with KLH-IA and treated with the vehicle. By 4 weeks after implantation tumor outgrowth in the treated groups was significantly decreased (p < 0.01, Fisher's Exact) relative to the control groups. Prior subcutaneous immunization was required to elicit antitumor activity of KLH-IA; thus, the mechanism of action is immune-mediated and not due to spurious interference with tumor implantation by intravesical instillations. Animals treated with a dissociated form of KLH exhibited decreased tumor outgrowth approaching, but not attaining, significance (p < 0.09, Fisher's Exact). A separate toxicity study in which KLH-IA was given subcutaneously (4 mg./kg.), intraperitoneally (40 mg./kg.), or intravesically (40 mg./kg.) disclosed no significant gross or histopathologic abnormalities except for mild-to-moderate papillary hyperplasia in all catheterized animals. These results establish the efficacy and safety of KLH-IA in mice and suggest that clinical trials for intravesical treatment of superficial bladder cancer may be warranted.

MeSH terms

  • Adjuvants, Immunologic / therapeutic use*
  • Adjuvants, Immunologic / toxicity
  • Animals
  • Dose-Response Relationship, Drug
  • Female
  • Hemocyanins / therapeutic use*
  • Hemocyanins / toxicity
  • Immunotherapy*
  • Male
  • Mice
  • Urinary Bladder Neoplasms / therapy*

Substances

  • Adjuvants, Immunologic
  • Hemocyanins
  • keyhole-limpet hemocyanin