Strategies for the Induction of Immune Tolerance to Enzyme Replacement Therapy in Mucopolysaccharidosis Type ICitation formats

  • External authors:
  • Arunabha Ghosh
  • Aiyin Liao
  • Claire O'Leary
  • Jean Mercer
  • Karen Tylee
  • Simon A. Jones

Standard

Strategies for the Induction of Immune Tolerance to Enzyme Replacement Therapy in Mucopolysaccharidosis Type I. / Ghosh, Arunabha; Liao, Aiyin; O'Leary, Claire; Mercer, Jean; Tylee, Karen; Goenka, Anu; Holley, Rebecca; Jones, Simon A.; Bigger, Brian W.

In: Molecular Therapy - Methods and Clinical Development, Vol. 13, 14.06.2019, p. 321-333.

Research output: Contribution to journalArticle

Harvard

Ghosh, A, Liao, A, O'Leary, C, Mercer, J, Tylee, K, Goenka, A, Holley, R, Jones, SA & Bigger, BW 2019, 'Strategies for the Induction of Immune Tolerance to Enzyme Replacement Therapy in Mucopolysaccharidosis Type I' Molecular Therapy - Methods and Clinical Development, vol. 13, pp. 321-333. https://doi.org/10.1016/j.omtm.2019.02.007

APA

Ghosh, A., Liao, A., O'Leary, C., Mercer, J., Tylee, K., Goenka, A., ... Bigger, B. W. (2019). Strategies for the Induction of Immune Tolerance to Enzyme Replacement Therapy in Mucopolysaccharidosis Type I. Molecular Therapy - Methods and Clinical Development, 13, 321-333. https://doi.org/10.1016/j.omtm.2019.02.007

Vancouver

Ghosh A, Liao A, O'Leary C, Mercer J, Tylee K, Goenka A et al. Strategies for the Induction of Immune Tolerance to Enzyme Replacement Therapy in Mucopolysaccharidosis Type I. Molecular Therapy - Methods and Clinical Development. 2019 Jun 14;13:321-333. https://doi.org/10.1016/j.omtm.2019.02.007

Author

Ghosh, Arunabha ; Liao, Aiyin ; O'Leary, Claire ; Mercer, Jean ; Tylee, Karen ; Goenka, Anu ; Holley, Rebecca ; Jones, Simon A. ; Bigger, Brian W. / Strategies for the Induction of Immune Tolerance to Enzyme Replacement Therapy in Mucopolysaccharidosis Type I. In: Molecular Therapy - Methods and Clinical Development. 2019 ; Vol. 13. pp. 321-333.

Bibtex

@article{49fe22114f004d9f8983051837da7e63,
title = "Strategies for the Induction of Immune Tolerance to Enzyme Replacement Therapy in Mucopolysaccharidosis Type I",
abstract = "Enzyme replacement therapy with laronidase is an established treatment for Mucopolysaccharidosis type I (MPS I), but its efficacy may be limited by the development of anti-drug antibodies, which inhibit cellular uptake of the enzyme. In a related disorder, infantile Pompe disease, immune tolerance induction with low-dose, short-course methotrexate appears to reduce antibody formation. We investigated a similar regimen using oral methotrexate in three MPS I patients. All patients developed anti-laronidase immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies, and they had clinically relevant levels of cellular uptake inhibition. We then explored several immune tolerance induction strategies in MPS I mice: (1) methotrexate, (2) combination of non-depleting anti-CD4 and anti-CD8 monoclonal antibodies, (3) methotrexate with anti-CD4 and anti-CD8 monoclonals, (4) anti-CD4 monoclonal, and (5) anti-CD8 monoclonal. Treated mice received 10 weekly laronidase injections, and laronidase was delivered with adjuvant on day 49 to further challenge the immune system. Most regimens were only partially effective at reducing antibody responses, but two courses of non-depleting anti-CD4 monoclonal antibody (mAb) ablated immune responses to laronidase in seven of eight MPS I mice (87.5{\%}), even after adjuvant stimulation. Immune tolerance induction with methotrexate does not appear to be effective in MPS I patients, but use of non-depleting anti-CD4 monoclonal is a promising strategy.",
keywords = "antiCD4, antiCD8, enzyme replacement therapy, haematopoietic stem cell transplantation, Hurler, immune tolerance, lysosomal storage disease, methotrexate, mucopolysaccharidosis",
author = "Arunabha Ghosh and Aiyin Liao and Claire O'Leary and Jean Mercer and Karen Tylee and Anu Goenka and Rebecca Holley and Jones, {Simon A.} and Bigger, {Brian W.}",
year = "2019",
month = "6",
day = "14",
doi = "10.1016/j.omtm.2019.02.007",
language = "English",
volume = "13",
pages = "321--333",
journal = "Molecular Therapy - Methods & Clinical Development",
issn = "2329-0501",
publisher = "Springer Nature",

}

RIS

TY - JOUR

T1 - Strategies for the Induction of Immune Tolerance to Enzyme Replacement Therapy in Mucopolysaccharidosis Type I

AU - Ghosh, Arunabha

AU - Liao, Aiyin

AU - O'Leary, Claire

AU - Mercer, Jean

AU - Tylee, Karen

AU - Goenka, Anu

AU - Holley, Rebecca

AU - Jones, Simon A.

AU - Bigger, Brian W.

PY - 2019/6/14

Y1 - 2019/6/14

N2 - Enzyme replacement therapy with laronidase is an established treatment for Mucopolysaccharidosis type I (MPS I), but its efficacy may be limited by the development of anti-drug antibodies, which inhibit cellular uptake of the enzyme. In a related disorder, infantile Pompe disease, immune tolerance induction with low-dose, short-course methotrexate appears to reduce antibody formation. We investigated a similar regimen using oral methotrexate in three MPS I patients. All patients developed anti-laronidase immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies, and they had clinically relevant levels of cellular uptake inhibition. We then explored several immune tolerance induction strategies in MPS I mice: (1) methotrexate, (2) combination of non-depleting anti-CD4 and anti-CD8 monoclonal antibodies, (3) methotrexate with anti-CD4 and anti-CD8 monoclonals, (4) anti-CD4 monoclonal, and (5) anti-CD8 monoclonal. Treated mice received 10 weekly laronidase injections, and laronidase was delivered with adjuvant on day 49 to further challenge the immune system. Most regimens were only partially effective at reducing antibody responses, but two courses of non-depleting anti-CD4 monoclonal antibody (mAb) ablated immune responses to laronidase in seven of eight MPS I mice (87.5%), even after adjuvant stimulation. Immune tolerance induction with methotrexate does not appear to be effective in MPS I patients, but use of non-depleting anti-CD4 monoclonal is a promising strategy.

AB - Enzyme replacement therapy with laronidase is an established treatment for Mucopolysaccharidosis type I (MPS I), but its efficacy may be limited by the development of anti-drug antibodies, which inhibit cellular uptake of the enzyme. In a related disorder, infantile Pompe disease, immune tolerance induction with low-dose, short-course methotrexate appears to reduce antibody formation. We investigated a similar regimen using oral methotrexate in three MPS I patients. All patients developed anti-laronidase immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies, and they had clinically relevant levels of cellular uptake inhibition. We then explored several immune tolerance induction strategies in MPS I mice: (1) methotrexate, (2) combination of non-depleting anti-CD4 and anti-CD8 monoclonal antibodies, (3) methotrexate with anti-CD4 and anti-CD8 monoclonals, (4) anti-CD4 monoclonal, and (5) anti-CD8 monoclonal. Treated mice received 10 weekly laronidase injections, and laronidase was delivered with adjuvant on day 49 to further challenge the immune system. Most regimens were only partially effective at reducing antibody responses, but two courses of non-depleting anti-CD4 monoclonal antibody (mAb) ablated immune responses to laronidase in seven of eight MPS I mice (87.5%), even after adjuvant stimulation. Immune tolerance induction with methotrexate does not appear to be effective in MPS I patients, but use of non-depleting anti-CD4 monoclonal is a promising strategy.

KW - antiCD4

KW - antiCD8

KW - enzyme replacement therapy

KW - haematopoietic stem cell transplantation

KW - Hurler

KW - immune tolerance

KW - lysosomal storage disease

KW - methotrexate

KW - mucopolysaccharidosis

UR - http://www.scopus.com/inward/record.url?scp=85063622671&partnerID=8YFLogxK

U2 - 10.1016/j.omtm.2019.02.007

DO - 10.1016/j.omtm.2019.02.007

M3 - Article

VL - 13

SP - 321

EP - 333

JO - Molecular Therapy - Methods & Clinical Development

JF - Molecular Therapy - Methods & Clinical Development

SN - 2329-0501

ER -