title: Immunotherapy with keyhole limpet hemocyanin: efficacy and safety in the MB-49 intravesical murine bladder tumor model.
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.
authors.affiliation: Organon Teknika/Biotechnology Research Institute, Rockville, Maryland 20850.
authors.forename: R D
authors.initials: RD
authors.lastname: Swerdlow
authors.forename: T L
authors.initials: TL
authors.lastname: Ratliff
authors.forename: M
authors.initials: M
authors.lastname: La Regina
authors.forename: J K
authors.initials: JK
authors.lastname: Ritchey
authors.forename: R F
authors.initials: RF
authors.lastname: Ebert
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use* / Q000633:toxicity; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006433:Hemocyanins / Q000627:therapeutic use* / Q000633:toxicity; D007167:Immunotherapy; D008297:Male; D051379:Mice; D001749:Urinary Bladder Neoplasms / Q000628:therapy*
chemical_list: D000276:Adjuvants, Immunologic; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin