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|Title:||A phase I biodistribution and pharmacokinetic trial of humanized monoclonal antibody Hu3s193 in patients with advanced epithelial cancers that express the Lewis-Y antigen.||Austin Authors:||Scott, Andrew M ;Tebbutt, Niall C ;Lee, Fook-Thean;Cavicchiolo, Tina;Liu, Zhanqi;Gill, Sanjeev;Poon, Aurora M T ;Hopkins, Wendie;Smyth, Fiona E;Murone, Carmel ;MacGregor, Duncan;Papenfuss, Anthony T;Chappell, Bridget;Saunder, Timothy H;Brechbiel, Martin W;Davis, Ian D;Murphy, Roger;Chong, Geoffrey ;Hoffman, Eric W;Old, Lloyd J||Affiliation:||Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch, Austin Hospital, Australia||Issue Date:||1-Jun-2007||Publication information:||Clinical Cancer Research; 13(11): 3286-92||Abstract:||We report a first-in-man trial of a humanized antibody (hu3S193) against the Le(y) antigen.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.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 40 mg/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)beta = 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.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.||Gov't Doc #:||17545534||URI:||http://ahro.austin.org.au/austinjspui/handle/1/10388||DOI:||10.1158/1078-0432.CCR-07-0284||Journal:||Clinical Cancer Research||URL:||https://pubmed.ncbi.nlm.nih.gov/17545534||Type:||Journal Article||Subjects:||Adult
Antibodies, Monoclonal.adverse effects.pharmacokinetics.therapeutic use
Antibodies, Monoclonal, Humanized
Lewis Blood-Group System.biosynthesis
|Appears in Collections:||Journal articles|
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