A statistical approach to improve compound screening in cell culture media

Eduard Puente-Massaguer; Llorenç Badiella; Sonia Gutiérrez-Granados; Laura Cervera; Francesc Gòdia

doi:10.1002/elsc.201800168

A statistical approach to improve compound screening in cell culture media

Eduard Puente-Massaguer, Llorenç Badiella, Sonia Gutiérrez-Granados, Laura Cervera, Francesc Gòdia

Producció científica: Contribució a revista › Article › Recerca

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Resum

La línia cel·lular d'ovari de hàmster xinès (CHO) s'utilitza àmpliament per a la producció de proteïnes recombinants degut a la seva alta capacitat i productivitat, així com altres línies cel·lulars derivades després del CHO. L'adaptació dels mitjans de cultiu cel·lular per a cada línia cel·lular específica és una clau per explotar aquestes característiques per a una generació de productes rendible i ràpida. La suplementació dels mitjans s'aborda generalment mitjançant enfocaments d'experiments amb un factor a la vegada o de disseny clàssic, però aquestes tècniques poden no ser prou eficients en fases preliminars de cribratge. En aquest estudi es va fer servir una nova estratègia que consisteix a doblar el disseny Plackett-Burman per augmentar el creixement cel·lular i la producció de trastuzumab de diferents línies cel·lulars CHO mitjançant suplementació amb compostos recombinants no animals. Es van poder detectar sinergies entre els compostos amb un nombre d'experiments reduït utilitzant aquesta metodologia en comparació amb dissenys factorials fraccionals més convencionals. En el cas particular que es presenta aquí, l'ús seqüencial d'aquest Plackett-Burman modificat en combinació amb un disseny de Box-Behnken va conduir a un augment d'1,5 vegades del creixement cel·lular (10 × 10 cèl·lules/mL) i dues vegades el títol de trastuzumab (122 mg/L) en cultiu per lots en suspensió. © 2019 WILEY-VCH Verlag GmbH

Idioma original	Anglès
Pàgines (de-a)	315-327
Nombre de pàgines	13
Revista	Engineering in life sciences
Volum	19
Número	4
DOIs	https://doi.org/10.1002/elsc.201800168
Estat de la publicació	Publicada - 1 d’abr. 2019

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10.1002/elsc.201800168

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title = "A statistical approach to improve compound screening in cell culture media",

abstract = "{\textcopyright} 2019 WILEY-VCH Verlag GmbH \& Co. KGaA, Weinheim The Chinese hamster ovary (CHO) cell line is widely used for the production of recombinant proteins due to its high growing capacity and productivity, as well as other cell lines derived later than CHO. Adapting cell culture media for each specific cell line is a key to exploit these features for cost effective and fast product generation. Media supplementation is generally addressed by means of one-factor-at-a-time or classical design of experiments approaches but these techniques may not be efficient enough in preliminary screening phases. In this study, a novel strategy consisting in folding over the Plackett–Burman design was used to increase cell growth and trastuzumab production of different CHO cell lines through supplementation with nonanimal recombinant compounds. Synergies between compounds could be detected with a reduced number of experiments by using this methodology in comparison to more conventional fractional factorial designs. In the particular case reported here, the sequential use of this modified Plackett–Burman in combination with a Box-Behnken design led to a 1.5-fold increase in cell growth (10 × 106 cells/mL) and a two-fold in trastuzumab titer (122 mg/L) in suspension batch culture.",

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author = "Eduard Puente-Massaguer and Lloren{\c c} Badiella and Sonia Guti{\'e}rrez-Granados and Laura Cervera and Francesc G{\`o}dia",

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AU - Puente-Massaguer, Eduard

AU - Badiella, Llorenç

AU - Gutiérrez-Granados, Sonia

AU - Cervera, Laura

AU - Gòdia, Francesc

PY - 2019/4/1

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N2 - © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim The Chinese hamster ovary (CHO) cell line is widely used for the production of recombinant proteins due to its high growing capacity and productivity, as well as other cell lines derived later than CHO. Adapting cell culture media for each specific cell line is a key to exploit these features for cost effective and fast product generation. Media supplementation is generally addressed by means of one-factor-at-a-time or classical design of experiments approaches but these techniques may not be efficient enough in preliminary screening phases. In this study, a novel strategy consisting in folding over the Plackett–Burman design was used to increase cell growth and trastuzumab production of different CHO cell lines through supplementation with nonanimal recombinant compounds. Synergies between compounds could be detected with a reduced number of experiments by using this methodology in comparison to more conventional fractional factorial designs. In the particular case reported here, the sequential use of this modified Plackett–Burman in combination with a Box-Behnken design led to a 1.5-fold increase in cell growth (10 × 106 cells/mL) and a two-fold in trastuzumab titer (122 mg/L) in suspension batch culture.

AB - © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim The Chinese hamster ovary (CHO) cell line is widely used for the production of recombinant proteins due to its high growing capacity and productivity, as well as other cell lines derived later than CHO. Adapting cell culture media for each specific cell line is a key to exploit these features for cost effective and fast product generation. Media supplementation is generally addressed by means of one-factor-at-a-time or classical design of experiments approaches but these techniques may not be efficient enough in preliminary screening phases. In this study, a novel strategy consisting in folding over the Plackett–Burman design was used to increase cell growth and trastuzumab production of different CHO cell lines through supplementation with nonanimal recombinant compounds. Synergies between compounds could be detected with a reduced number of experiments by using this methodology in comparison to more conventional fractional factorial designs. In the particular case reported here, the sequential use of this modified Plackett–Burman in combination with a Box-Behnken design led to a 1.5-fold increase in cell growth (10 × 106 cells/mL) and a two-fold in trastuzumab titer (122 mg/L) in suspension batch culture.

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KW - GENERATION

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KW - PLACKETT-BURMAN DESIGN

KW - PRODUCTIVITY

KW - RECOMBINANT PROTEINS

KW - RESPONSE-SURFACE METHODOLOGY

KW - TRANSFECTION

KW - best-fit Box-Behnken

KW - folded-over Plackett-Burman

KW - medium optimization

KW - trastuzumab

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JO - Engineering in life sciences

JF - Engineering in life sciences

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ER -

A statistical approach to improve compound screening in cell culture media

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