A phase II study of a 5T4 oncofoetal antigen tumour-targeted superantigen (ABR-214936) therapy in patients with advanced renal cell carcinoma.

2.50
Hdl Handle:
http://hdl.handle.net/10541/70321
Title:
A phase II study of a 5T4 oncofoetal antigen tumour-targeted superantigen (ABR-214936) therapy in patients with advanced renal cell carcinoma.
Authors:
Shaw, David M; Connolly, Noel B; Patel, P M; Kilany, S; Hedlund, Gunnar; Nordle, O; Forsberg, G; Zweit, Jamal; Stern, Peter L; Hawkins, Robert E
Abstract:
In a phase II study, 43 renal cell carcinoma patients were treated with individualised doses of ABR-214936; a fusion of a Fab recognising the antigen 5T4, and Staphylococcal enterotoxin A. Drug was given intravenously on 4 consecutive days, treatment was repeated 1 month later. Treatment was associated with moderate fever and nausea, but well tolerated. Of 40 evaluable patients, 28 had disease control at 2 months, and at 4 months, one patient showed partial response (PR) and 16 patients stable disease. Median survival, with minimum follow-up of 26 months was 19.7 months with 13 patients alive to date. Stratification by the Motzer's prognostic criteria highlights prolonged survival compared to published expectation. Patients receiving higher drug exposure had greater disease control and lived almost twice as long as expected, whereas the low-exposure patients survived as expected. Sustained interleukin-2 (IL-2) production after a repeated injection appears to be a biomarker for clinical effect, as the induced-IL-2 level on the day 2 of treatment correlated with survival. The high degree of disease control and the prolonged survival suggest that this treatment can be effective. These findings will be used in the trial design for the next generation of drug, with reduced antigenicity and toxicity.
Affiliation:
Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester M20 4BX, UK. dshaw@picr.man.ac.uk
Citation:
A phase II study of a 5T4 oncofoetal antigen tumour-targeted superantigen (ABR-214936) therapy in patients with advanced renal cell carcinoma. 2007, 96 (4):567-74 Br. J. Cancer
Journal:
British Journal of Cancer
Issue Date:
26-Feb-2007
URI:
http://hdl.handle.net/10541/70321
DOI:
10.1038/sj.bjc.6603567
PubMed ID:
17285137
Type:
Article
Language:
en
ISSN:
0007-0920
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorShaw, David M-
dc.contributor.authorConnolly, Noel B-
dc.contributor.authorPatel, P M-
dc.contributor.authorKilany, S-
dc.contributor.authorHedlund, Gunnar-
dc.contributor.authorNordle, O-
dc.contributor.authorForsberg, G-
dc.contributor.authorZweit, Jamal-
dc.contributor.authorStern, Peter L-
dc.contributor.authorHawkins, Robert E-
dc.date.accessioned2009-06-12T13:45:40Z-
dc.date.available2009-06-12T13:45:40Z-
dc.date.issued2007-02-26-
dc.identifier.citationA phase II study of a 5T4 oncofoetal antigen tumour-targeted superantigen (ABR-214936) therapy in patients with advanced renal cell carcinoma. 2007, 96 (4):567-74 Br. J. Canceren
dc.identifier.issn0007-0920-
dc.identifier.pmid17285137-
dc.identifier.doi10.1038/sj.bjc.6603567-
dc.identifier.urihttp://hdl.handle.net/10541/70321-
dc.description.abstractIn a phase II study, 43 renal cell carcinoma patients were treated with individualised doses of ABR-214936; a fusion of a Fab recognising the antigen 5T4, and Staphylococcal enterotoxin A. Drug was given intravenously on 4 consecutive days, treatment was repeated 1 month later. Treatment was associated with moderate fever and nausea, but well tolerated. Of 40 evaluable patients, 28 had disease control at 2 months, and at 4 months, one patient showed partial response (PR) and 16 patients stable disease. Median survival, with minimum follow-up of 26 months was 19.7 months with 13 patients alive to date. Stratification by the Motzer's prognostic criteria highlights prolonged survival compared to published expectation. Patients receiving higher drug exposure had greater disease control and lived almost twice as long as expected, whereas the low-exposure patients survived as expected. Sustained interleukin-2 (IL-2) production after a repeated injection appears to be a biomarker for clinical effect, as the induced-IL-2 level on the day 2 of treatment correlated with survival. The high degree of disease control and the prolonged survival suggest that this treatment can be effective. These findings will be used in the trial design for the next generation of drug, with reduced antigenicity and toxicity.en
dc.language.isoenen
dc.subjectCancer Antigensen
dc.subjectRenal Canceren
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAntigens, Neoplasm-
dc.subject.meshCarcinoma, Renal Cell-
dc.subject.meshDisease Progression-
dc.subject.meshDose-Response Relationship, Drug-
dc.subject.meshDrug Toxicity-
dc.subject.meshEnterotoxins-
dc.subject.meshFemale-
dc.subject.meshFollow-Up Studies-
dc.subject.meshHumans-
dc.subject.meshInjections, Intravenous-
dc.subject.meshInterleukin-2-
dc.subject.meshKidney Neoplasms-
dc.subject.meshMale-
dc.subject.meshMembrane Glycoproteins-
dc.subject.meshMiddle Aged-
dc.subject.meshPredictive Value of Tests-
dc.subject.meshPrognosis-
dc.subject.meshRecombinant Fusion Proteins-
dc.subject.meshSurvival Rate-
dc.subject.meshTreatment Outcome-
dc.titleA phase II study of a 5T4 oncofoetal antigen tumour-targeted superantigen (ABR-214936) therapy in patients with advanced renal cell carcinoma.en
dc.typeArticleen
dc.contributor.departmentPaterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester M20 4BX, UK. dshaw@picr.man.ac.uken
dc.identifier.journalBritish Journal of Canceren

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