Anti-tumor effects of tumor necrosis factor alone or combined with radiotherapy.
Recombinant human tumor necrosis factor (rHuTNF) was investigated for its ability to increase the response of murine tumors to ionizing radiation. Both multiple i.v. administrations of rHuTNF and local tumor irradiation caused a significant delay in tumor growth. The effect of treatment with both agents combined was greater than the additive effect of the individual treatments. Furthermore, rHuTNF significantly increased tumor radiocurability, as assessed by the TCD50 assay. rHuTNF was not cytotoxic to tumor cells, nor did it affect their radiosensitivity. The in vivo anti-tumor effect of rHuTNF and its augmentation of tumor radioresponse were mediated through indirect mechanisms, either immunological or non-immunological. rHuTNF was also effective in reducing the damaging effect of ionizing radiation on bone-marrow progenitor cells, which could increase the therapeutic advantage of the rHuTNF-radiotherapy combination. These experiments suggest that rHuTNF is potentially beneficial in combination with radiotherapy.
Sersa
G
G
Department of Experimental Radiotherapy, University of Texas, M.D. Anderson Hospital and Tumor Institute, Houston 77030.
Willingham
V
V
Milas
L
L
D000818:Animals; D002460:Cell Line; D003114:Colony-Forming Units Assay; D003131:Combined Modality Therapy; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy / Q000532:radiotherapy; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000532:radiotherapy; D051379:Mice; D008809:Mice, Inbred C3H; D011838:Radiation-Sensitizing Agents; D011879:Radiotherapy Dosage; D011994:Recombinant Proteins / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*; D014410:Tumor Stem Cell Assay
D011838:Radiation-Sensitizing Agents; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha