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Titolo:
Upregulation of antitumor immunity by IL-12 gene-transfected AK-5 tumor cells in vivo
Autore:
Nandakumar, KS; Rao, KL; Pardhasaradhi, BVV; Khar, A;
Indirizzi:
Ctr Cellular & Mol Biol, Hyderabad 500007, Andhra Pradesh, India Ctr Cellular & Mol Biol Hyderabad Andhra Pradesh India 500007 desh, India
Titolo Testata:
CYTOKINES CELLULAR & MOLECULAR THERAPY
fascicolo: 1, volume: 5, anno: 1999,
pagine: 7 - 14
SICI:
1368-4736(199903)5:1<7:UOAIBI>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
NATURAL-KILLER-CELL; SPONTANEOUS IMMUNOLOGICAL REGRESSION; IN-VIVO; RAT HISTIOCYTOMA; ADENOCARCINOMA CELLS; CYTOKINE RESPONSE; MURINE TUMORS; FAS LIGAND; INTERLEUKIN-12; EXPRESSION;
Keywords:
IL-12; gene transfection; tumor regression;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Khar, A Ctr Cellular & Mol Biol, Uppal Rd, Hyderabad 500007, Andhra Pradesh, India Ctr Cellular & Mol Biol Uppal Rd Hyderabad Andhra Pradesh India 500007
Citazione:
K.S. Nandakumar et al., "Upregulation of antitumor immunity by IL-12 gene-transfected AK-5 tumor cells in vivo", CYTOK CELL, 5(1), 1999, pp. 7-14

Abstract

We have earlier demonstrated a significant role for IL-12 in the regression of a rat histiocytic tumor, AK-5. In order to analyze further the antitumor immunity induced by interleukin (It)-12, we have established IL-12-secreting tumor cell clones by gene transfection. Significant enhancement in thelytic potential of splenocytes by the culture supernatants containing IL-12 demonstrated retention of biological activity by the tumor-cell-derived cytokine. Athymic nude mice transplanted subcutaneously with tumor cells engineered to secret IL-12 showed a significant reduction in tumor size, with enhanced antibody-dependent cellular cytotoxicity. Analysis of the serum samples from animals injected with the IL-12 gene-transfected AK-5 cells on different days revealed a significant increase in circulatory IL-12, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and antitumor antibodies, ail of which contributed to the reduction in tumor mass. The enhanced proliferative capacity of splenocytes from these animals indicated the presence of highly activated immune cells in vivo. Similarly, intraperitoneal transplantation of IL-12 gene-transfected tumor cells in syngeneic Wistar rats induced a significant increase in cellular cytotoxicity, with a concomitantreduction in cirulatory IL-12 (p40) protein. Administration of antibodies to IL-12 and IFN-gamma reduced the expression of the costimulatory molecules B7.1 and B7.2 and the cytolytic effecters granzyme B and Fas-L, suggesting their involvement in IFN-gamma-dependent antitumor immune response induced by IL-12. The present study thus demonstrates that IL-12 gene therapy could be among the promising approaches for an effective cancer therapy.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 11/07/20 alle ore 04:18:06