ABSTRACT
In this paper we describe the generation of antibody dependent cellular cytotoxicity against a murine renal cell carcinoma. Using human recombinant interleukin-2 and in vitro adherence to plastic, we generated lymphokine activated killer and adherent lymphokine activated killer cells. Adherent lymphokine activated killer cells had significant (p less than 0.05) higher unrestricted cytotoxicity than LAK cells. Using a rabbit antibody against Renca developed in our laboratory, we induced significant (p less than 0.01) antibody dependent cellular cytotoxicity using fresh spleen, lymphokine activated killer and adherent lymphokine activated killer cells. The strongest antibody dependent cellular cytotoxicity killing was mediated by adherent lymphokine activated killer cells and was restricted only to the renal cell carcinoma target. Using FACS cell surface analysis and antibody and complement depletion of selected effector cell subsets, we also demonstrate that the antibody dependent cellular cytotoxicity effector cell population consists of asialoGM1+ Lyt 2.1- natural killer cells. This first description of antibody dependent cellular cytotoxicity against renal cell carcinoma by activated natural killer cells suggests a novel method for more efficient use of cytotoxic effector cells against this type of cancer.
Subject(s)
Carcinoma, Renal Cell/immunology , Cytotoxicity, Immunologic , Kidney Neoplasms/immunology , Lymphocytes/immunology , Animals , Antibody-Dependent Cell Cytotoxicity , Antigens, Differentiation/analysis , Carcinoma, Renal Cell/therapy , Kidney Neoplasms/therapy , Killer Cells, Lymphokine-Activated/immunology , Killer Cells, Natural/immunology , Mice , Mice, Inbred BALB C , PhenotypeABSTRACT
Six groups of two cynomolgus monkeys were treated with escalating intravesicular doses of recombinant human tumor necrosis factor (rHuTNF) for a 6 week interval. The doses of rHuTNF ranged from 10 ng to 1 mg and were instilled weekly. Two monkeys had instillation of saline only and served as controls. The monkeys were weighed and temperatures determined before, immediately after, and 2 days following each treatment. Cystoscopic examination was performed 2 days after each treatment and blood samples were obtained. At the conclusion of the study, animals were killed and necropsy was performed. There was no observable toxicity from treatment with rHuTNF. There was no difference between treated and control monkeys with respect to temperature, weight, or blood measurements. No drug-induced alteration in bladder morphology was found by either cystoscopic or microscopic pathologic examination.
Subject(s)
Tumor Necrosis Factor-alpha/toxicity , Administration, Intravesical , Animals , Female , Liver/drug effects , Liver/pathology , Macaca fascicularis , Recombinant Proteins/toxicity , Tumor Necrosis Factor-alpha/administration & dosage , Urinary Bladder/drug effects , Urinary Bladder/pathologySubject(s)
Cystoscopy/veterinary , Macaca fascicularis/anatomy & histology , Macaca/anatomy & histology , Tumor Necrosis Factor-alpha/pharmacology , Urinary Bladder/anatomy & histology , Urinary Catheterization/veterinary , Animals , Female , Recombinant Proteins/pharmacology , Urinary Bladder/drug effectsABSTRACT
Stage-specific embryonic antigen-1 (SSEA-1) was localized on paraffin embedded, formalin fixed specimens of human renal tumors by immunoperoxidase staining using a monoclonal antibody. Of 19 renal cell carcinoma (RCC) samples tested, 12 were positive for SSEA-1; SSEA-1 was also found on distinct elements in two samples of Wilms' tumor. No correlation was found between expression of SSEA-1, and RCC morphology or pattern of growth. Because SSEA-1 is found on proximal tubules in the normal kidney, these results support the hypothesis that RCC arises from the cells of the proximal tubule. Furthermore, since greater than 60% of the RCCs examined expressed SSEA-1, this antigen may prove to be a useful target for immunolocation or therapy of metastatic RCC.
