Postoperative immunotherapy of murine C1300-neuroblastoma.
Low-dose cyclophosphamide (CY) is an immunomodulating agent that down-regulates T suppressor cell function. This study investigates postoperative immunotherapy with CY as an alternate treatment for advanced immunogenic tumors such as neuroblastoma that typically respond poorly to traditional high-dose chemotherapy. A/J mice with 1.5-cm subcutaneous C1300-neuroblastoma (C1300-NB) tumors were divided into the following treatment groups: I, untreated (n = 14); II, 85% tumor resection (n = 18); III, sham-operated (n = 18); IV, multiple-dose CY (n = 6); V, 85% resection and single-dose CY (n = 14); VI, 85% resection and multiple-dose CY (n = 14). CY (100 mg/kg, intraperitoneally) was given initially 24 hours post-operatively to groups IV, V, and VI. Groups IV and VI also received weekly maintenance doses of 25 mg/kg CY. Results showed significantly increased survival (log-rank test) in CY-treated groups (IV, V, VI) compared with control groups (I,II,III). Cures were observed only in groups receiving partial resection plus CY (V, 7%; VI, 29%). Although surgical debulking of tumor alone (II) did not enhance survival, the procedure normalized depressed total lymphocyte counts and the subpopulation of Lyt 2,3+ (T suppressor/cytolytic cells) in the immediate postoperative period during which immunotherapy with CY was instigated. This may have contributed to the success of CY immunotherapy. To characterize the tumor-host immune interaction, additional studies were performed. Results showed the following. (1) Mice cured by debulking plus CY (from groups V and VI) could not be successfully reimplanted with C1300-NB, demonstrating immunologic mediation by CY.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pediatric Surgery, Children's Hospital of Buffalo, University of Buffalo, NY 14222.
C L
CL
Fowler
S P
SP
Brooks
J E
JE
Rossman
D R
DR
Cooney
D000818:Animals; D000961:Antilymphocyte Serum; D003520:Cyclophosphamide / Q000008:administration & dosage*; D000939:Epitopes; D005260:Female; D007167:Immunotherapy; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D051379:Mice; D008805:Mice, Inbred A; D008815:Mice, Inbred Strains; D009447:Neuroblastoma / Q000276:immunology / Q000601:surgery / Q000628:therapy*; D011379:Prognosis; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000473:pathology
D000961:Antilymphocyte Serum; D000939:Epitopes; D003520:Cyclophosphamide