title: From laboratory to Phase I/II cancer trials with recombinant biotherapeutics.
abstract: Many promising recombinant cancer medicines are generated by academic research and increasing the number of these products that are translated into the clinic will increase the pipeline of new therapies. Recombinant proteins for use in Phase I/II cancer trials must be produced to standards of Good Manufacturing Practice (GMP) in compliance with EU law. This can be a major obstacle for translating experimental products to clinical reality especially when there is no established process or prior experience with GMP. Here, we illustrate the principals of GMP with a step-by-step guide and we show that GMP can be achieved on a relatively small scale in the researchers own institution. The process is exemplified with an antibody-based therapeutic expressed in the yeast Pichia pastoris. The purified product has been used safely in patients and the principles are applicable to any recombinant protein required for Phase I/II cancer trials.
authors.affiliation: Cancer Research UK Targeting and Imaging Group, Department of Oncology, UK.
authors.forename: B
authors.initials: B
authors.lastname: Tolner
authors.forename: L
authors.initials: L
authors.lastname: Smith
authors.forename: T
authors.initials: T
authors.lastname: Hillyer
authors.forename: J
authors.initials: J
authors.lastname: Bhatia
authors.forename: P
authors.initials: P
authors.lastname: Beckett
authors.forename: L
authors.initials: L
authors.lastname: Robson
authors.forename: S K
authors.initials: SK
authors.lastname: Sharma
authors.forename: N
authors.initials: N
authors.lastname: Griffin
authors.forename: W
authors.initials: W
authors.lastname: Vervecken
authors.forename: R
authors.initials: R
authors.lastname: Contreras
authors.forename: R B
authors.initials: RB
authors.lastname: Pedley
authors.forename: R H J
authors.initials: RH
authors.lastname: Begent
authors.forename: K A
authors.initials: KA
authors.lastname: Chester
mesh_terms: D000970:Antineoplastic Agents / Q000592:standards* / Q000627:therapeutic use; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004059:Diffusion of Innovation; D015195:Drug Design; D004345:Drug Industry / Q000592:standards; D004512:Education, Pharmacy; D005285:Fermentation; D006031:Glycosylation; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D024382:Professional Role; D011786:Quality Control; D011994:Recombinant Proteins / Q000592:standards* / Q000627:therapeutic use; D013678:Technology, Pharmaceutical / Q000592:standards; D015003:Yeasts
chemical_list: D000970:Antineoplastic Agents; D011994:Recombinant Proteins