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Development of a panel of highly sensitive, equivalent assays for detection of antibody responses to velaglucerase alfa or imiglucerase enzyme replacement therapy in patients with Gaucher disease.
J Immunol Methods. 2011 Oct 28; 373(1-2):45-53.JI

Abstract

Anti-drug antibodies are elicited by virtually all therapeutic proteins, and standardized assays are required for clinical monitoring of patients as well as for comparing antibody response to different therapeutic proteins in clinical trials. Velaglucerase alfa and imiglucerase are enzyme replacement therapies for the long-term treatment of type 1 Gaucher disease, a lysosomal storage disease resulting from an inherited deficiency of the enzyme glucocerebrosidase. We used state-of-the-art tools to develop a panel of assays for detection and characterization of antibody responses to velaglucerase alfa and imiglucerase. Highly-sensitive, direct bridging electrochemiluminescence screening assays were developed using samples from treatment-naïve individuals with type 1 Gaucher disease to set cut points. A mouse anti-glucocerebrosidase monoclonal antibody used as a calibrator was shown to have similar affinity and binding kinetics for anti-velaglucerase alfa and anti-imiglucerase antibodies. A quantitative radioimmunoprecipitation assay for IgG antibodies was developed to eliminate false-positives from the highly sensitive screening assay. Using 59 samples from treatment-naïve individuals with type 1 Gaucher disease, the confirmatory cut points were calculated to be 1.42 ng/mL for anti-velaglucerase alfa antibodies and 3.23 ng/mL for anti-imiglucerase antibodies. Isotype-specific indirect electrochemiluminescence assays were developed for IgE, IgA, and IgM subclasses. The IgE subclass assay was shown to be more sensitive than the confirmatory assay using sheep anti-glucocerebrosidase polyclonal antibody cross-linked with fragments specific to human IgE, with cut points for anti-velaglucerase alfa or anti-imiglucerase antibodies determined to be 0.53 and 0.55 ng/mL, respectively. An assay that detects inhibition in vitro of velaglucerase alfa and imiglucerase hydrolysis of a synthetic substrate in the presence of antibodies was developed to test for neutralizing antibodies. Using 52 individual healthy human donor samples and 35 samples from treatment-naïve individuals with type 1 Gaucher disease, cut points for the velaglucerase alfa and imiglucerase neutralizing antibody assays were determined to be 20%, such that a sample with greater than 20% inhibition of enzyme activity in the presence of antibodies was considered positive for neutralizing antibodies. In conclusion, highly sensitive and equivalent methods were developed and validated to directly compare antibody response to velaglucerase alfa and imiglucerase treatments in patients with Gaucher disease, and may contribute to future internationally standardized assays for antibody detection in patients with Gaucher disease.

Authors+Show Affiliations

Department of Bioanalytical and Biomarker Development, Shire Human Genetic Therapies, 300 Shire Way, Lexington, MA 02421, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21846471

Citation

Séllos-Moura, Márcia, et al. "Development of a Panel of Highly Sensitive, Equivalent Assays for Detection of Antibody Responses to Velaglucerase Alfa or Imiglucerase Enzyme Replacement Therapy in Patients With Gaucher Disease." Journal of Immunological Methods, vol. 373, no. 1-2, 2011, pp. 45-53.
Séllos-Moura M, Barzegar S, Pan L, et al. Development of a panel of highly sensitive, equivalent assays for detection of antibody responses to velaglucerase alfa or imiglucerase enzyme replacement therapy in patients with Gaucher disease. J Immunol Methods. 2011;373(1-2):45-53.
Séllos-Moura, M., Barzegar, S., Pan, L., Shi, P., Oommen, S., Durant, J., & Ruiz, J. A. (2011). Development of a panel of highly sensitive, equivalent assays for detection of antibody responses to velaglucerase alfa or imiglucerase enzyme replacement therapy in patients with Gaucher disease. Journal of Immunological Methods, 373(1-2), 45-53. https://doi.org/10.1016/j.jim.2011.07.020
Séllos-Moura M, et al. Development of a Panel of Highly Sensitive, Equivalent Assays for Detection of Antibody Responses to Velaglucerase Alfa or Imiglucerase Enzyme Replacement Therapy in Patients With Gaucher Disease. J Immunol Methods. 2011 Oct 28;373(1-2):45-53. PubMed PMID: 21846471.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Development of a panel of highly sensitive, equivalent assays for detection of antibody responses to velaglucerase alfa or imiglucerase enzyme replacement therapy in patients with Gaucher disease. AU - Séllos-Moura,Márcia, AU - Barzegar,Samad, AU - Pan,Luying, AU - Shi,Philip, AU - Oommen,Susan, AU - Durant,Judith, AU - Ruiz,Juan A, Y1 - 2011/08/06/ PY - 2011/01/21/received PY - 2011/07/01/revised PY - 2011/07/25/accepted PY - 2011/8/18/entrez PY - 2011/8/19/pubmed PY - 2012/1/28/medline SP - 45 EP - 53 JF - Journal of immunological methods JO - J. Immunol. Methods VL - 373 IS - 1-2 N2 - Anti-drug antibodies are elicited by virtually all therapeutic proteins, and standardized assays are required for clinical monitoring of patients as well as for comparing antibody response to different therapeutic proteins in clinical trials. Velaglucerase alfa and imiglucerase are enzyme replacement therapies for the long-term treatment of type 1 Gaucher disease, a lysosomal storage disease resulting from an inherited deficiency of the enzyme glucocerebrosidase. We used state-of-the-art tools to develop a panel of assays for detection and characterization of antibody responses to velaglucerase alfa and imiglucerase. Highly-sensitive, direct bridging electrochemiluminescence screening assays were developed using samples from treatment-naïve individuals with type 1 Gaucher disease to set cut points. A mouse anti-glucocerebrosidase monoclonal antibody used as a calibrator was shown to have similar affinity and binding kinetics for anti-velaglucerase alfa and anti-imiglucerase antibodies. A quantitative radioimmunoprecipitation assay for IgG antibodies was developed to eliminate false-positives from the highly sensitive screening assay. Using 59 samples from treatment-naïve individuals with type 1 Gaucher disease, the confirmatory cut points were calculated to be 1.42 ng/mL for anti-velaglucerase alfa antibodies and 3.23 ng/mL for anti-imiglucerase antibodies. Isotype-specific indirect electrochemiluminescence assays were developed for IgE, IgA, and IgM subclasses. The IgE subclass assay was shown to be more sensitive than the confirmatory assay using sheep anti-glucocerebrosidase polyclonal antibody cross-linked with fragments specific to human IgE, with cut points for anti-velaglucerase alfa or anti-imiglucerase antibodies determined to be 0.53 and 0.55 ng/mL, respectively. An assay that detects inhibition in vitro of velaglucerase alfa and imiglucerase hydrolysis of a synthetic substrate in the presence of antibodies was developed to test for neutralizing antibodies. Using 52 individual healthy human donor samples and 35 samples from treatment-naïve individuals with type 1 Gaucher disease, cut points for the velaglucerase alfa and imiglucerase neutralizing antibody assays were determined to be 20%, such that a sample with greater than 20% inhibition of enzyme activity in the presence of antibodies was considered positive for neutralizing antibodies. In conclusion, highly sensitive and equivalent methods were developed and validated to directly compare antibody response to velaglucerase alfa and imiglucerase treatments in patients with Gaucher disease, and may contribute to future internationally standardized assays for antibody detection in patients with Gaucher disease. SN - 1872-7905 UR - https://www.unboundmedicine.com/medline/citation/21846471/Development_of_a_panel_of_highly_sensitive_equivalent_assays_for_detection_of_antibody_responses_to_velaglucerase_alfa_or_imiglucerase_enzyme_replacement_therapy_in_patients_with_Gaucher_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-1759(11)00204-3 DB - PRIME DP - Unbound Medicine ER -