Arthur Y. Elliott

Antibody induction of lymphocyte-mediated cytotoxicity against human transitional-cell carcinomas of the urinary tract.

Abstract Serum from a patient with transitional-cell carcinoma of the urinary tract, which induced lymphocyte-mediated cytotoxicity against the carcinoma, was studied to determine the active factor and characterize its mode of action. The active serum factor was an IgG immunoglobulin that induced cytotoxicity only in the presence of effector cells (lymphocytes) and did not require the presence of complement. Contact between the IgG and a tumor-associated antigen appeared to be required before cytotoxicity could be induced in the lymphocyte. The IgG induced lymphocytes from donors with and without transitional-cell carcinoma to become cytotoxic against cells derived from transitional-cell carcinoma of the renal pelvis, ureter, and bladder but not against normal adult or embryonic cells or against renal-cell-carcinoma cells. These characteristics indicate that the active serum factor is a lymphocyte-dependent antibody that is directed against an antigen associated with transitional-cell carcinoma. (N Engl J...

In vitro cultivation of human renal cell cancer

SummaryTwo cell lines derived from primary human renal-cell cancers (RCC) have been established and characterized. Cell line 786-O has been in culture for longer than 1 year and has been subcultured more than 50 times. It has a doubling time of 45 hr and a hypertriploid karyotype and possesses a Y chromosome. Cell line 769-P also has been in culture for longer than 1 year. It has been subcultured 50 times and has a doubling time of 35 hr and a hypodiploid karyotype. Cells from both lines are epithelial, and they produce tumors in the cheek pouches of immunosuppressed hamsters. Neither cell line is contaminated withMycoplasma. Cells of the two lines can be distinguished from HeLa cells both by their karyotypes and by the mobility patterns of their isoenzymes of glucose-6-phosphate dehydrogenase.

In vitro cultivation of human renal cell cancer. I. Establishment of cells in culture.

SummaryA technique for initiating and propagating epithelial cell cultures of human renal cell cancer and adjacent nontumor kidney is described. Seventy-five percent of the tumors and 79% of the adjacent kidney specimens cultured with this method have shown initial outgrowth and have been subcultured at least once. Two renal cell cancer cultures initiated by this method have now been in continuous culture more than 6 months, have been subcultured 27 and 19 times, and now appear to be stable lines.The ability to establish long-term in vitro cultures of human renal cell cancers will facilitate studies concerning the immunoreactivity, cholesterol metabolism, the isolation of renal-cell-cancer-specific antigens, and in vitro chemotherapy testing and will further our understanding of the basic biology of human renal cell cancer.

Cell mediated cytotoxicity against human transitional cell carcinomas of the genitourinary tract.

Lymphocytes from 48 patients with transitional cell carcinoma (TCC) of the genitourinary tract and 51 control patients without TCC were tested for cell mediated immunity to TCC‐derived target cells in a microcytotoxicity assay. Eighty‐three percent of the TCC patients had lymphocytes cytotoxic to TCC target cells, as opposed to 31% of controls. Lymphocytes from patients with TCC of the renal pelvis (TCC‐P) were cytotoxic to target cells derived from TCC of the bladder (TCC‐B). Conversely, TCC‐B lymphocytes were cytotoxic to TCC‐P target cells. The incidence of cytotoxicity among control patients against TCC and renal cell carcinoma target cells increased with age and demonstrated the importance of control population selection in assessing the specificity of human tumor immunity assays. However, the incidence of anti‐TCC cytotoxicity by lymphocytes from TCC donors (83%) was still significantly greater than that of age‐matched control donors (38%) (p < 0.001).

Isolation of RNA Virus from Papillary Tumors of the Human Renal Pelvis

Virus particles were detected by electron microscopy in three papillary cancers of the human renal pelvis. Similar particles were seen in cells from all three tumors in primary culture. An RNA virus was isolated from these tumors. The serum of tumor patients contains neutralizing antibodies against virus isolated from two of the tumors. Initial studies suggest that this agent is not a known human RNA virus.

Technique for cultivation of transitional epithelium from mammalian urinary bladder

SummaryA technique for initiating cultures of epithelial (urothelial) cells from mammalian urinary bladder has been described. Urothelial cells obtained by this method have been used to support replication of viruses and as controls for immunological, biochemical, chromosome, and electron microscopy studies. Both light and electron microscopic studies of cultured cells suggest that they are epithelial and not a mixed culture.

Changes in Cell-mediated Cytotoxicity during the Clinical Course of Patients with Bladder Carcinoma

The conventional cell-mediated cytotoxicity assay was modified so that more useful estimates of cell-mediated immunity to transitional cell carcimoma of the urinary tract could be obtained. With this modified assay changes in the levels of cell-mediated immunity in transitional cell carcinoma patients to transitional cell carcinoma target cells were measured during the clinical course. Initial results from a small number of patients with invasive and non-invasive tumors showed that anti-transitional cell carcinoma cell-mediated immunity increased after the tumor was removed and during administration of Bacillus Calmette-Guerin.

Lymphocyte Antibody Interaction in Cytotoxicity Against Human Transitional Cell Carcinoma

The interaction of antibodies and lymphocytes in their immune reaction against human transitional cell carcinomas was studied using the in vitro microcytotoxicity assay. A non-complement dependent, IgG antibody was detected in the serum of occasional transitional cell carcinoma patients, which induced cytotoxicity against transitional cell carcinoma target cells by lymphocytes from donors with and without transitional cell carcinoma. The observation that lymphocytes from transitional cell carcinoma donors were more sensitive to activation by this anti-transitional cell carcinoma, lymphocyte dependent antibody is compatible with the hypothesis that the surface of lymphocytes from some transitional cell carcinoma donors is coated in vivo with an anti-transitional cell carcinoma lymphocyte dependent antibody and that this antibody may be a significant factor in immunity to transitional cell carcinomas of the urinary tract.