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Details

Autor(en) / Beteiligte
Titel
A Phase I Biodistribution and Pharmacokinetic Trial of Humanized Monoclonal Antibody Hu3s193 in Patients with Advanced Epithelial Cancers that Express the Lewis-Y Antigen
Ist Teil von
  • Clinical cancer research, 2007-06, Vol.13 (11), p.3286-3292
Ort / Verlag
Philadelphia, PA: American Association for Cancer Research
Erscheinungsjahr
2007
Quelle
MEDLINE
Beschreibungen/Notizen
  • Purpose: We report a first-in-man trial of a humanized antibody (hu3S193) against the Le y antigen. Experimental Design: Patients with advanced Le y -positive cancers received four infusions of hu3S193 at weekly intervals, with four dose levels (5, 10, 20, and 40 mg/m 2 ). The first infusion of hu3S193 was trace labeled with Indium-111, and biodistribution, pharmacokinetics, tumor uptake, and immune response were evaluated in all patients. Results: A total of 15 patients (7 male/8 female; age range, 42-76 years; 6 breast, 8 colorectal cancer, and 1 non–small-cell lung cancer) were entered into the study. Transient grade 1 to 2 nausea and vomiting was observed following infusion of hu3S193 at the 40mg/m 2 dose level only. There was one episode of dose-limiting toxicity with self-limiting Common Toxicity Criteria grade 3 elevated alkaline phosphatase observed in one patient with extensive liver metastases. The biodistribution of 111 In-hu3S193 showed no evidence of any consistent normal tissue uptake, and 111 In-hu3S193 uptake was observed in cutaneous, lymph node, and hepatic metastases. Hu3S193 displayed a long serum half-life (T 1/2 β = 189.63 ± 62.17 h). Clinical responses consisted of 4 patients with stable disease and 11 patients with progressive disease, although one patient experienced a 89% decrease in a lymph node mass, and one patient experienced inflammatory symptoms in cutaneous metastases, suggestive of a biological effect of hu3S193. No immune responses (human anti-human antibody) to hu3S193 were observed. Conclusion: Hu3S193 is well tolerated and selectively targets tumors, and the long half-life and biological function in vivo of this antibody makes it an attractive potential therapy for patients with Le y -expressing cancers.

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