Enhanced anti-tumor effects of recombinant human tumor necrosis factor plus VP-16 on metastatic renal cell carcinoma in a xenograft model.
A nude mouse renal subcapsular and subcutaneous implantation xenograft model utilizing the SN12C human renal carcinoma cell line was investigated. In the absence of treatment, renal subcapsular implantation of SN12C resulted in metastatic spread (lung, liver and lymph nodes) and death of all animals. Radical nephrectomy of the tumor-bearing kidney after various periods of tumor implantation demonstrated that surgery alone after 18 days of tumor growth resulted in no statistically significant increase in survival with 100% of the nephrectomized animals succumbing to local recurrence and distant metastases. Recombinant human tumor necrosis factor (rTNF) and VP16 (etoposide), both well known cytotoxic and cytostatic anticancer agents, were tested singly and in combination against this metastatic model of human renal adenocarcinoma. Single agent rTNF or VP16 therapy after radical nephrectomy demonstrated only minimal efficacy with no significant decrease in local recurrence and distant metastases as compared to nephrectomy only control animals. In contrast, the combination of rTNF plus VP16 when given after nephrectomy resulted in a significant decrease in local recurrence and no gross evidence of metastasis in any animal. Subcutaneously growing SN12C tumor nodules were also treated with the same rTNF, VP16 and combination regimens. Regression in tumor size was noted only in the combination treatment group. rTNF or VP16, as single agents, demonstrated only slight growth inhibition that was not statistically significant. These results suggest that by combining TNF plus VP16, a synergistic enhancement of antineoplastic activity against local as well as metastatic human renal cell carcinoma can be produced.
Burgers
J K
JK
James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.
Marshall
F F
FF
Isaacs
J T
JT
D000818:Animals; D002292:Carcinoma, Renal Cell / Q000556:secondary / Q000628:therapy*; D003131:Combined Modality Therapy; D005047:Etoposide / Q000627:therapeutic use*; D006801:Humans; D007680:Kidney Neoplasms / Q000628:therapy*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D009392:Nephrectomy; D011994:Recombinant Proteins / Q000627:therapeutic use; D012074:Remission Induction; D013370:Subrenal Capsule Assay; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D005047:Etoposide