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Titolo:
Phase I study of single, escalating doses of a superantigen-antibody fusion protein (PNU-214565) in patients with advanced colorectal or pancreatic carcinoma
Autore:
Nielsen, SE; Zeuthen, J; Lund, B; Persson, B; Alenfall, J; Hansen, HH;
Indirizzi:
Univ Copenhagen Hosp, Rigshosp, Finsen Ctr, Dept Oncol 5072, DK-2100 Copenhagen, Denmark Univ Copenhagen Hosp Copenhagen Denmark DK-2100 2100 Copenhagen, Denmark Danish Canc Soc, Inst Canc Biol, Dept Tumor Cell Biol, Copenhagen, DenmarkDanish Canc Soc Copenhagen Denmark Tumor Cell Biol, Copenhagen, Denmark Pharmacia & Upjohn Inc, Dept Clin Res, Lund, Sweden Pharmacia & Upjohn Inc Lund Sweden ohn Inc, Dept Clin Res, Lund, Sweden
Titolo Testata:
JOURNAL OF IMMUNOTHERAPY
fascicolo: 1, volume: 23, anno: 2000,
pagine: 146 - 153
SICI:
1524-9557(200001)23:1<146:PISOSE>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
TARGETED SUPERANTIGENS; MONOCLONAL-ANTIBODIES; T-CELLS; THERAPY; CANCER; IMMUNOTHERAPY; LYMPHOCYTES; CA-19-9; CA-50;
Keywords:
targeted immunotherapy; superantigen; fusion protein; phase I clinical trial;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
16
Recensione:
Indirizzi per estratti:
Indirizzo: Nielsen, SE Univ Copenhagen Hosp, Rigshosp, Finsen Ctr, Dept Oncol 5072, Blegdamsvej 9, DK-2100 Copenhagen, Denmark Univ Copenhagen Hosp Blegdamsvej 9 Copenhagen Denmark DK-2100
Citazione:
S.E. Nielsen et al., "Phase I study of single, escalating doses of a superantigen-antibody fusion protein (PNU-214565) in patients with advanced colorectal or pancreatic carcinoma", J IMMUNOTH, 23(1), 2000, pp. 146-153

Abstract

To develop a T-cell-based therapy for carcinomas, the superantigen staphylococcal enterotoxin A (SEA) was supplied with tumor specificity by means ofa recombinant fusion of the Fab fragment of the monoclonal antibody C242 recognizing human colorectal (CRC) and pancreatic carcinomas (PC). Using this Fab-SEA fusion protein (PNU-214565), potent cytotoxicity by activation ofT cells can be obtained in the targeted area. Twenty-one patients with CRCand 3 with PC were treated with single, escalating doses of PNU-214565 to establish the maximum tolerated dose (MTD) and to define toxicities. The doses ranged from 0.01 ng/kg to 4.0 ng/kg with three patients at each dose level, except for the dose of 1.5 ng/kg with which six patients were treated because of dose-limiting toxicity. Adverse events (AE) were transient: 13 patients experienced mild to moderate fever. In one patient, a grade 3 feverwas followed by a grade 2 hypotension. Other mild or moderate AEs were fatigue, nausea, vomiting, diarrhea, and abdominal pain. No significant hematological toxicity occurred. Immune activation was highly variable with strong activity in peripheral blood seen only in two patients at the dosage level 1.5 ng/kg. They showed pronounced elevations of interleukin-2 (IL-2), IL-6, tumor necrosis factor-alpha, and interferon-gamma, 3-5 hours after the start of infusion. In one patient, IL-2 and IL-6 increased substantially (2,925 U/mL and 32,000 U/mL) concomitantly with grade 3 fever and transient grade 2 neutropenia, grade 2 lymphopenia, and grade 2 monocytopenia. In conclusion, a single 3-hour infusion of PNU-214565 could be safely administered up to 4 ng/kg. MTD was nor determined. Instead, a repeat-dose trial was initiated starting at 0.5 ng/kg, considered safe in this trial, with the objective of defining the MTD.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 14/07/20 alle ore 13:15:43