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Titolo:
ANTITUMOR EFFICACY OF ADENOCARCINOMA CELLS ENGINEERED TO PRODUCE INTERLEUKIN-12 (IL-12) OR OTHER CYTOKINES COMPARED WITH EXOGENOUS IL-12
Autore:
CAVALLO F; SIGNORELLI P; GIOVARELLI M; MUSIANI P; MODESTI A; BRUNDA MJ; COLOMBO MP; FORNI G;
Indirizzi:
OSPED SAN LUIGI GONZAGA,DIPARTIMENTO SCI CLIN & BIOL I-10043 ORBASSANO ITALY UNIV TURIN,DIPARTIMENTO SCI CLIN & BIOL I-10124 TURIN ITALY UNIV TURIN,CTR CNR IMMUNOGENET & ONCOL SPERIMENTALE I-10124 TURIN ITALY UNIV CHIETI,IST PATOL UMANA & MED SOCIALE CHIETI ITALY HOFFMANN LA ROCHE INC,DEPT ONCOL NUTLEY NJ 07110 IST NAZL TUMORI I-20133 MILAN ITALY
Titolo Testata:
Journal of the National Cancer Institute
fascicolo: 14, volume: 89, anno: 1997,
pagine: 1049 - 1058
Fonte:
ISI
Lingua:
ENG
Soggetto:
MOUSE MAMMARY ADENOCARCINOMA; COLONY-STIMULATING FACTOR; GAMMA-INTERFERON GENE; IN-VIVO; MEMORY RESPONSE; TUMOR REJECTION; MURINE TUMORS; IMMUNITY; INHIBITION; LYMPHOCYTE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
46
Recensione:
Indirizzi per estratti:
Citazione:
F. Cavallo et al., "ANTITUMOR EFFICACY OF ADENOCARCINOMA CELLS ENGINEERED TO PRODUCE INTERLEUKIN-12 (IL-12) OR OTHER CYTOKINES COMPARED WITH EXOGENOUS IL-12", Journal of the National Cancer Institute, 89(14), 1997, pp. 1049-1058

Abstract

Background: Numerous animal model studies have examined the ability of genetically engineered tumor cells to release cytokines and to elicit an immune memory against the parental tumor, Often only a single cytokine is studied, and few comparative studies have been conducted. Purpose: We evaluated the antitumor efficacy of adenocarcinoma cells engineered to release interleukin (IL)-12 in a mouse model system, The efficacy of this cytokine was compared with that of other cytokines released by engineered adenocarcinoma cells and that of exogenous IL-12 administered both locally and intraperitoneally. Methods: BALB/cAnCr micewere inoculated with syngeneic parental mammary adenocarcinoma (TSA) cells in quantities sufficient to lead to tumors in all inoculated mice, TSA cells engineered to release IL-12 (TSA-IL12) were also injectedinto normal and selectively immunosuppressed BALB/cAnCr mice, Tumor incidence, growth, and rejection patterns were evaluated by the measurement of neoplastic masses and by the study of the histologic and ultrastructural features of the tumor site, The effects of local or intraperitoneal administration of recombinant IL-12 (rIL-12) on tumor-bearinganimals were also studied, Results: Most mice rejected TSA-IL12 cellsthrough a CDS-positive, T-lymphocyte-dependent reaction associated with macrophage infiltration, vessel damage, and necrosis, The systemic immunity of mice that had rejected TSA-IL12 cells to a subsequent challenge with parental TSA cells was less efficient than that elicited byTSA cells engineered to release IL-4 or IL-10 but equivalent to that elicited by TSA cells engineered to release IL-2, IL-7, and interferonalfa, Compared with TSA cells engineered to produce other cytokines, TSA-IL12 cells were the most efficient in curing mice with establishedTSA tumors; injection of 0.1 million proliferating cells contralaterally to the tumor growth area cured five of 15 mice bearing 1-day-old tumors; injection of the same dose of proliferating cells into the tumor growth area cured two of 20 tumor-bearing mice, However, two 5-day courses with a nontoxic dose (0.1 mu g) of rIL-12 given intraperitoneally cured a similar proportion of these animals (six of 20), Only two of 20 mice with 7-day-old TSA tumors were cured by vaccination with proliferating TSA-IL12 cells, whereas 24 of 30 mice with such tumors werecured by intraperitoneal administration of rIL-12, Conclusions: TSA cells engineered to release IL-12 are rejected by most mice; the ensuing immune memory for TSA parental cells, however, was less efficient than that elicited by proliferating TSA cells engineered to release other cytokines (e.g., IL-4, IL-10, and possibly interferon gamma), The immune reaction elicited by TSA-IL12 cells was the most efficient in curing mice with established TSA tumors; notably though, the same or a better cure rate was obtained with rIL-12 given intraperitoneally.

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Documento generato il 30/09/20 alle ore 09:16:08