title: A phase II study of a 5T4 oncofoetal antigen tumour-targeted superantigen (ABR-214936) therapy in patients with advanced renal cell carcinoma.
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.
authors.affiliation: Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester M20 4BX, UK. dshaw@picr.man.ac.uk
authors.forename: D M
authors.initials: DM
authors.lastname: Shaw
authors.forename: N B
authors.initials: NB
authors.lastname: Connolly
authors.forename: P M
authors.initials: PM
authors.lastname: Patel
authors.forename: S
authors.initials: S
authors.lastname: Kilany
authors.forename: G
authors.initials: G
authors.lastname: Hedlund
authors.forename: O
authors.initials: O
authors.lastname: Nordle
authors.forename: G
authors.initials: G
authors.lastname: Forsberg
authors.forename: J
authors.initials: J
authors.lastname: Zweit
authors.forename: P L
authors.initials: PL
authors.lastname: Stern
authors.forename: R E
authors.initials: RE
authors.lastname: Hawkins
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions; D004768:Enterotoxins / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007275:Injections, Intravenous; D007376:Interleukin-2 / Q000096:biosynthesis; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: C522592:ABR-214936; D000951:Antigens, Neoplasm; D004768:Enterotoxins; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; C031192:oncofetal antigens; C063709:trophoblastic glycoprotein 5T4, human; C026066:enterotoxin A, Staphylococcal