Combined preoperative and postoperative immunotherapy for murine C1300 neuroblastoma.
Preoperative treatment of murine C1300-neuroblastoma (C1300) with triple immunotherapy using low-dose cyclophosphamide (CY), retinyl palmitate (RP), and interleukin-2 (IL2), followed by tumor resection leads to significant initial tumor control and prolonged survival. However, because long-term tumor recurrence is 67%, the efficacy of continued postoperative immunotherapy is now evaluated. Thirty-two A/J mice with 1 cm subcutaneous C1300 tumors were treated for 13 days with CY-100 mg/kg, intraperitoneally (IP), on day 2 of treatment then 25 mg/kg on day 9, RP-2500 IU IP 2 x/week, and IL2 1.6 x 10(5) U IP BID on days 4 to 9 and 11 to 13. On day 14, mice were divided into five treatment groups: (1) OP (operated-tumor resection, n = 6); (2) OP+CY (resection and postoperative CY, n = 7); (3) OP+CY+RP (resection and postoperative CY+RP, n = 7); (4) OP+CY+RP+IL2 (resection and postoperative CY+RP+IL2, n = 7); and (5) CY+RP+IL2 (continued CY+RP+IL2 with no resection, n = 5). Survival and postoperative tumor recurrence were followed for 60 days. The cure rates were group 1 33% (2/6), group 2 43% (3/7), group 3 29% (2/7), group 4 71% (5/7), and group 5 20% (1/5). After surgery, tumors that recurred did so in 8 to 22 days, with no statistical difference noted between groups. MHC class I antigenic expression of tumors resected on day 14 and recurrent tumors was determined with monoclonal antibodies and flow cytometry. In tumors resected on day 14, class I expression measured by mean fluorescence, was 374.8 +/- 27.40.(ABSTRACT TRUNCATED AT 250 WORDS)
Fowler
C L
CL
Section of Pediatric Surgery, University of Kentucky Medical Center, Lexington 40536-0084.
Brooks
S P
SP
Rossman
J E
JE
Cooney
D R
DR
D000818:Animals; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004224:Diterpenes; D004359:Drug Therapy, Combination; D005260:Female; D005805:Genes, MHC Class I / Q000235:genetics; D007165:Immunosuppression Therapy; D007376:Interleukin-2 / Q000627:therapeutic use*; D051379:Mice; D008954:Models, Biological; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D009447:Neuroblastoma / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011182:Postoperative Care; D011300:Preoperative Care; D000084562:Retinyl Esters; D015996:Survival Rate; D013997:Time Factors; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000627:therapeutic use
D004224:Diterpenes; D007376:Interleukin-2; D000084562:Retinyl Esters; D014801:Vitamin A; C014794:retinol palmitate; D003520:Cyclophosphamide