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Author Correction: CD98hc is a target for brain delivery of biotherapeutics.

ABSTRACT:

SUBMITTER: Chew KS

PROVIDER: S-EPMC10484993 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Author Correction: CD98hc is a target for brain delivery of biotherapeutics.

Chew Kylie S KS Wells Robert C RC Moshkforoush Arash A Chan Darren D Lechtenberg Kendra J KJ Tran Hai L HL Chow Johann J Kim Do Jin DJ Robles-Colmenares Yaneth Y Srivastava Devendra B DB Tong Raymond K RK Tong Mabel M Xa Kaitlin K Yang Alexander A Zhou Yinhan Y Akkapeddi Padma P Annamalai Lakshman L Bajc Kaja K Blanchette Marie M Cherf Gerald Maxwell GM Earr Timothy K TK Gill Audrey A Huynh David D Joy David D Knight Kristen N KN Lac Diana D Leung Amy Wing-Sze AW Lexa Katrina W KW Liau Nicholas P D NPD Becerra Isabel I Malfavon Mario M McInnes Joseph J Nguyen Hoang N HN Lozano Edwin I EI Pizzo Michelle E ME Roche Elysia E Sacayon Patricia P Calvert Meredith E K MEK Daneman Richard R Dennis Mark S MS Duque Joseph J Gadkar Kapil K Lewcock Joseph W JW Mahon Cathal S CS Meisner René R Solanoy Hilda H Thorne Robert G RG Watts Ryan J RJ Zuchero Y Joy Yu YJY Kariolis Mihalis S MS

Nature communications 20230907 1

PMID: 37679403

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CD98hc is a target for brain delivery of biotherapeutics.

Project description:Brain exposure of systemically administered biotherapeutics is highly restricted by the blood-brain barrier (BBB). Here, we report the engineering and characterization of a BBB transport vehicle targeting the CD98 heavy chain (CD98hc or SLC3A2) of heterodimeric amino acid transporters (TVCD98hc). The pharmacokinetic and biodistribution properties of a CD98hc antibody transport vehicle (ATVCD98hc) are assessed in humanized CD98hc knock-in mice and cynomolgus monkeys. Compared to most existing BBB platforms targeting the transferrin receptor, peripherally administered ATVCD98hc demonstrates differentiated brain delivery with markedly slower and more prolonged kinetic properties. Specific biodistribution profiles within the brain parenchyma can be modulated by introducing Fc mutations on ATVCD98hc that impact FcγR engagement, changing the valency of CD98hc binding, and by altering the extent of target engagement with Fabs. Our study establishes TVCD98hc as a modular brain delivery platform with favorable kinetic, biodistribution, and safety properties distinct from previously reported BBB platforms.

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CD98hc is a target for brain delivery of biotherapeutics

Project description:Brain exposure of systemically administered biotherapeutics is highly restricted by the blood-brain barrier (BBB). Here, we report the engineering and characterization of a BBB transport vehicle targeting the CD98 heavy chain (CD98hc or SLC3A2) of heterodimeric amino acid transporters (TV^CD98hc). The pharmacokinetic and biodistribution properties of a CD98hc antibody transport vehicle (ATV^CD98hc) are assessed in humanized CD98hc knock-in mice and cynomolgus monkeys. Compared to most existing BBB platforms targeting the transferrin receptor, peripherally administered ATVCD98hc demonstrates differentiated brain delivery with markedly slower and more prolonged kinetic properties. Specific biodistribution profiles within the brain parenchyma can be modulated by introducing Fc mutations on ATV^CD98hc that impact FcgR engagement, changing the valency of CD98hc binding, and by altering the extent of target engagement with Fabs. Our study establishes TV^CD98hc as a modular brain delivery platform with favorable kinetic, biodistribution, and safety properties distinct from previously reported BBB platforms.

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