Retardation of postsurgical metastases with the use of extracted tumor-specific transplantation antigens and cyclophosphamide.
In a 3-methylcholanthrene [(MCA) CAS: 56-49-5]-induced tumor model of C3H/HeJ mice excision of a growing primary tumor decreased concomitant immunity and facilitated experimental lung metastases. Administration of tumor-specific transplantation antigens extracted from viable MCA-F cells with the use of single-phase (2.5%) 1-butanol [crude butanol extract (CBE)] augmented immunity after resection of the primary MCA-F tumor. Two weeks after footpad inoculation of 2 X 10(5) MCA-F cells, the tumor-bearing limbs were amputated and the mice were challenged subsequently with 5 X 10(4) cells of clone-9-4, a metastatic variant of MCA-F, via the tail vein. Whereas treatment with either 50 micrograms CBE sc or 20 mg cyclophosphamide (CY)/kg ip failed to retard lung colonization, combination therapy with the two agents reduced the incidence of lung colonies by 69.8% (26.5 vs. 8; P less than .001) compared with the incidence in the surgery-alone group and by 55.5% (18 vs. 8; P less than .001) compared with the incidence in the group treated with surgery and CY. Furthermore, the combined effects of CBE and CY were immunologically specific: The combined therapy with the non-cross-reactive MCA-D-CBE did not protect against iv challenge with clone-9-4. Treatment with antigenic extracts induced a 21.4% (4.2 vs. 3.3%) decrease in the ratio of Lyt 1+:Lyt 2+ cells in the spleens of tumor-resected mice, which suggested restoration to normal levels. Therefore, in the combined regimen, antigen may induce specific activation of helper lymphocytes, while CY inhibits activation of suppressor cells.
D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005260:Female; D006649:Histocompatibility Antigens / Q000008:administration & dosage*; D007167:Immunotherapy; D051379:Mice; D008809:Mice, Inbred C3H; D009362:Neoplasm Metastasis / Q000473:pathology*; D012513:Sarcoma, Experimental / Q000276:immunology / Q000473:pathology / Q000601:surgery* / Q000628:therapy*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000951:Antigens, Neoplasm; D006649:Histocompatibility Antigens; C029237:tumor-associated transplantation antigen; D003520:Cyclophosphamide