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Titolo:
Mechanism of antitumor activity of a single-chain interleukin-12 IgG3 antibody fusion protein (mscIL-12.her2.IgG3)
Autore:
Peng, LS; Penichet, ML; Dela Cruz, JS; Sampogna, SL; Morrison, SL;
Indirizzi:
Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA Univ Calif Los Angeles Los Angeles CA USA 90095 Los Angeles, CA 90095 USA Univ Calif Los Angeles, Dept Neurobiol, Los Angeles, CA 90095 USA Univ Calif Los Angeles Los Angeles CA USA 90095 Los Angeles, CA 90095 USA Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA Univ Calif Los Angeles Los Angeles CA USA 90095 Los Angeles, CA 90095 USA
Titolo Testata:
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH
fascicolo: 9, volume: 21, anno: 2001,
pagine: 709 - 720
SICI:
1079-9907(200109)21:9<709:MOAAOA>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECOMBINANT HUMAN INTERLEUKIN-12; METASTATIC BREAST-CANCER; IN-VIVO; T-CELLS; INTERFERON-GAMMA; IFN-GAMMA; PHASE-II; IL-12; MICE; EXPRESSION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Morrison, SL Univ Calif Los Angeles, Dept Microbiol & Mol Genet, 405 Hilgard Ave, Los Angeles, CA 90095 USA Univ Calif Los Angeles 405 Hilgard Ave Los Angeles CA USA 90095
Citazione:
L.S. Peng et al., "Mechanism of antitumor activity of a single-chain interleukin-12 IgG3 antibody fusion protein (mscIL-12.her2.IgG3)", J INTERF CY, 21(9), 2001, pp. 709-720

Abstract

We have constructed an antibody interleukin-12 (IL-12) fusion protein (mscIL-12.her2.IgG3) that demonstrates significant antitumor activity against the murine carcinoma CT26-expressing human HER2/neu. We now report that thisantitumor activity is dose dependent and comparable to or better than recombinant murine IL-12 (rMuIL-12) using subcutaneous and metastatic models ofdisease. The antitumor activity of mscIL-12.her2.IgG3 is reduced in Rag2 knockout mice, suggesting that T cells play a role in tumor rejection. In SCID-beige mice, the antitumor activity is further reduced, suggesting that natural killer (NK) cells or macrophages or both are also important. The isotype of the antibody response to HER2/neu is consistent with a switch from a Th2 to a Th1 immune response and the infiltration of mononuclear cell in tumors from mice treated with mscIL-12.her2.IgG3. Immunohistochemistry reveals that mscIL-12.her2.IgG3 is antiangiogenic. Thus, the mechanism of the antitumor activity exhibited by mscIL-12.her2.IgG3 is highly complex and involves a combination of T and NK cell activity, a switch to a Th1 immune response, and antiantiogenic activity. This is the first study comparing the in viva antitumor activity of an antibody-IL-12 fusion protein and free IL-12. Our results suggest that antibody-IL-12 fusion proteins may be useful for the treatment of human cancer.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/04/20 alle ore 23:25:23