Low-dose interferon gamma renders neuroblastoma more susceptible to interleukin-2 immunotherapy.
Neuroblastoma remains a common and deadly childhood tumor, resistant to both surgical and chemo/radiotherapeutic intervention in its advanced stages. The role of immunotherapy in such cancers has yet to be defined. In previous work, we found that the addition of interferon gamma (IFN-gamma) to 3-day in vitro tissue cultures of the murine neuroblastoma C1300, led not only to the tumor's increased cell surface expression of the immunologically important major histocompatibility complex (MHC) class I antigen, but also to an increased susceptibility of such modified tumor to subsequent lymphokine activated killer (LAK) cell lysis. In this study, we sought to determine the in vivo applicability of these findings. Initial dose-response studies helped define a regimen of rIFN-gamma's administration that upregulated MHC class I without activating host natural killer (NK) activity. A/J mice bearing 7-day-old subcutaneous C1300 were randomized to receive daily morning injections of either 0, 25,000, 50,000, or 100,000 U of rIFN-gamma intraperitoneally for 6 days. Animals were killed at days 3, 6, and 9 after initiation of rIFN-gamma therapy, and tumors were excised, digested, and stained for both MHC class I and II expression. At the time of sacrifice, splenocytes from each animal were tested for NK cytotoxicity toward YAC (an NK-sensitive lymphoma) and C1300. These studies defined 3 days of therapy with 25,000 U as a "priming" dose that increased expression of class I with minimal impact on NK activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Sigal
R K
RK
Harrison Department of Surgical Research, University of Pennsylvania School of Medicine, Philadelphia.
Lieberman
M D
MD
Reynolds
J V
JV
Shou
J
J
Ziegler
M M
MM
Daly
J M
JM
D000704:Analysis of Variance; D000818:Animals; D003602:Cytotoxicity, Immunologic; D004305:Dose-Response Relationship, Drug; D007167:Immunotherapy; D007371:Interferon-gamma / Q000008:administration & dosage*; D007376:Interleukin-2 / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D009447:Neuroblastoma / Q000628:therapy*; D015996:Survival Rate
D007376:Interleukin-2; D007371:Interferon-gamma