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1996-02-26
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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).