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Titolo:
Mannan mucin-1 peptide immunization: Influence of cyclophosphamide and theroute of injection
Autore:
Karanikas, V; Thynne, G; Mitchell, P; Ong, CS; Gunawardana, D; Blum, R; Pearson, J; Lodding, J; Pietersz, G; Broadbent, R; Tait, B; McKenzie, IFC;
Indirizzi:
Austin Res Inst, Immunol & Vaccine Lab, Heidelberg, Vic 3084, Australia Austin Res Inst Heidelberg Vic Australia 3084 elberg, Vic 3084, Australia Royal Melbourne Hosp, Tissue Typing Lab, Melbourne, Vic, Australia Royal Melbourne Hosp Melbourne Vic Australia , Melbourne, Vic, Australia
Titolo Testata:
JOURNAL OF IMMUNOTHERAPY
fascicolo: 2, volume: 24, anno: 2001,
pagine: 172 - 183
SICI:
1524-9557(200103/04)24:2<172:MMPIIO>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACTIVE SPECIFIC IMMUNOTHERAPY; IMMUNE-RESPONSES; FUSION PROTEIN; BREAST-CANCER; SIALYL-TN; PHASE-I; MUC1; CELL; ADENOCARCINOMA; ANTIGEN;
Keywords:
clinical trials; vaccine; cancer; immunotherapy;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
21
Recensione:
Indirizzi per estratti:
Indirizzo: McKenzie, IFC Austin Res Inst, Immunol & Vaccine Lab, Studley Rd, Heidelberg, Vic 3084, Australia Austin Res Inst Studley Rd Heidelberg Vic Australia3084 lia
Citazione:
V. Karanikas et al., "Mannan mucin-1 peptide immunization: Influence of cyclophosphamide and theroute of injection", J IMMUNOTH, 24(2), 2001, pp. 172-183

Abstract

The mucin MUC1 is greatly increased in breast cancer and is a potential target for immunotherapy. In mice, MUC1 conjugated to oxidized mannan (MUC1-mannan fusion protein [M-FP]) targets the mannose receptor and induces a high frequency of cytotoxic T lymphocytes and anti-tumor responses. On this basis, three phase I trials were performed in patients with adenocarcinoma toevaluate the toxicity and the immunologic responses to mannan MUC1. Forty-one patients with metastatic or locally advanced carcinoma of the breast (trial 1), colon (trial 2), and various adenocarcinomas (trial 3) received increasing doses of M-FP (1 to 300 mug). The immunizations were given at weekly intervals (weeks 1 to 3) and repeated in weeks 7 to 9. Cyclophosphamide (to increase cellular immunity) was given on weeks 1 and 3. M-FP was given intramuscularly in trial 1 and intraperitoneally in trial 2. No toxic effects occurred, and delayed-type hypersensitivity responses were present only as a microscopic lymphocytic infiltration. Overall, approximately 60% of the patients had high-titer MUC1 immunoglobulin G1 antibody responses, with the intraperitoneal route yielding approximately 10-fold higher responses. Cellular responses (proliferation, cytotoxic T cells, or CD8 T cells secreting tumor necrosis factor-alpha and interferon-gamma in response to MUC1 stimulation in vitro) were found in 28% of the patients, which was similar to that seen without cyclophosphamide. In most patients, disease progressed, but in five it remained stable. In addition, there were no objective responses. M-FP is not toxic and induces immune responses that were amplified by the intraperitoneal route of immunization. Cyclophosphamide was of no benefit.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/04/20 alle ore 02:41:06