Document 0746
 DOCN  M9620746
 TI    B7-1 and interleukin 12 synergistically induce effective antitumor
       immunity.
 DT    9602
 AU    Coughlin CM; Wysocka M; Kurzawa HL; Lee WM; Trinchieri G; Eck SL;
       Biomedical Graduate Program, University of Pennsylvania,; Philadelphia
       19104, USA.
 SO    Cancer Res. 1995 Nov 1;55(21):4980-7. Unique Identifier : AIDSLINE
       MED/96046606
 AB    Enhanced host rejection of tumor cells is the primary goal of cancer
       immunotherapy and, in many murine tumor models, has been accomplished by
       engineering cells to express B7 costimulatory molecules or creating an
       environment rich in certain cytokines. We examined the effect of tumor
       cell B7-1 expression and administered recombinant interleukin 12 (IL-12)
       on the syngeneic host response to rapidly growing, poorly immunogenic
       SCK mammary carcinoma cells and to more slowly growing, immunogenic
       K1735 melanoma cells. Whereas B7-1 expression induced rejection of K1735
       cells in 78% of mice, and IL-12 induced rejection in 38%, B7-1
       expression induced rejection of SCK cells in only 28% of mice, and IL-12
       induced rejection in none. The relative ineffectiveness of either B7-1
       or IL-12 alone to induce rejection of SCK cells led us to combine the
       two manipulations. This resulted in rejection of SCK cells in 74% of
       mice and dramatically delayed tumor development in the remainder. Tumor
       rechallenge studies indicated that the surviving mice developed specific
       immunity to wild-type SCK cells. Lymphocyte subset ablation and
       IFN-gamma depletion studies indicated that rejection of SCK tumor cells
       brought about by the synergistic effects of B7-1 and IL-12 is mediated
       by a rapidly developing, systemic antitumor immune response that is
       dependent on the presence of both CD8+ and CD4+ T cells and involves
       IFN-gamma. Additionally, the synergistic effect of B7-1 expression and
       IL-12 administration is capable of inducing rejection of control SCK
       tumors simultaneously established in the opposite flank. The efficacy of
       B7-1 and IL-12 in inducing protective immunity against a poorly
       immunogenic, aggressive murine tumor indicates that this combination is
       particularly effective at producing a potent antitumor immune response
       that may be of therapeutic benefit.
 DE    Animal  Antigens, CD80/*THERAPEUTIC USE  Comparative Study  CD4-Positive
       T-Lymphocytes/IMMUNOLOGY  CD8-Positive T-Lymphocytes/IMMUNOLOGY  Drug
       Synergism  Female  Graft Rejection/IMMUNOLOGY  Immunity, Natural
       Immunotherapy  Interferon Type II/BIOSYNTHESIS
       Interleukin-12/*THERAPEUTIC USE  Mammary Neoplasms,
       Experimental/*IMMUNOLOGY/*PREVENTION & CONTROL/  THERAPY  Melanoma,
       Experimental/*IMMUNOLOGY/*PREVENTION & CONTROL  Mice  Mice, Inbred A
       Mice, Inbred C3H  Neoplasm Transplantation/*IMMUNOLOGY  Sensitivity and
       Specificity  Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).