Tags

Type your tag names separated by a space and hit enter

Abeta targets of the biosimilar antibodies of Bapineuzumab, Crenezumab, Solanezumab in comparison to an antibody against N‑truncated Abeta in sporadic Alzheimer disease cases and mouse models.
Acta Neuropathol 2015; 130(5):713-29AN

Abstract

Solanezumab and Crenezumab are two humanized antibodies targeting Amyloid-β (Aβ) which are currently tested in multiple clinical trials for the prevention of Alzheimer's disease. However, there is a scientific discussion ongoing about the target engagement of these antibodies. Here, we report the immunohistochemical staining profiles of biosimilar antibodies of Solanezumab, Crenezumab and Bapineuzumab in human formalin-fixed, paraffin-embedded tissue and human fresh frozen tissue. Furthermore, we performed a direct comparative immunohistochemistry analysis of the biosimilar versions of the humanized antibodies in different mouse models including 5XFAD, Tg4-42, TBA42, APP/PS1KI, 3xTg. The staining pattern with these humanized antibodies revealed a surprisingly similar profile. All three antibodies detected plaques, cerebral amyloid angiopathy and intraneuronal Aβ in a similar fashion. Remarkably, Solanezumab showed a strong binding affinity to plaques. We also reaffirmed that Bapineuzumab does not recognize N-truncated or modified Aβ, while Solanezumab and Crenezumab do detect N-terminally modified Aβ peptides Aβ4-42 and pyroglutamate Aβ3-42. In addition, we compared the results with the staining pattern of the mouse NT4X antibody that recognizes specifically Aβ4-42 and pyroglutamate Aβ3-42, but not full-length Aβ1-42. In contrast to the biosimilar antibodies of Solanezumab, Crenezumab and Bapineuzumab, the murine NT4X antibody shows a unique target engagement. NT4X does barely cross-react with amyloid plaques in human tissue. It does, however, detect cerebral amyloid angiopathy in human tissue. In Alzheimer mouse models, NT4X detects intraneuronal Aβ and plaques comparable to the humanized antibodies. In conclusion, the biosimilar antibodies Solanezumab, Crenezumab and Bapineuzumab strongly react with amyloid plaques, which are in contrast to the NT4X antibody that hardly recognizes plaques in human tissue. Therefore, NT4X is the first of a new class of therapeutic antibodies.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

26467270

Citation

Bouter, Yvonne, et al. "Abeta Targets of the Biosimilar Antibodies of Bapineuzumab, Crenezumab, Solanezumab in Comparison to an Antibody Against N‑truncated Abeta in Sporadic Alzheimer Disease Cases and Mouse Models." Acta Neuropathologica, vol. 130, no. 5, 2015, pp. 713-29.
Bouter Y, Lopez Noguerola JS, Tucholla P, et al. Abeta targets of the biosimilar antibodies of Bapineuzumab, Crenezumab, Solanezumab in comparison to an antibody against N‑truncated Abeta in sporadic Alzheimer disease cases and mouse models. Acta Neuropathol. 2015;130(5):713-29.
Bouter, Y., Lopez Noguerola, J. S., Tucholla, P., Crespi, G. A., Parker, M. W., Wiltfang, J., ... Bayer, T. A. (2015). Abeta targets of the biosimilar antibodies of Bapineuzumab, Crenezumab, Solanezumab in comparison to an antibody against N‑truncated Abeta in sporadic Alzheimer disease cases and mouse models. Acta Neuropathologica, 130(5), pp. 713-29.
Bouter Y, et al. Abeta Targets of the Biosimilar Antibodies of Bapineuzumab, Crenezumab, Solanezumab in Comparison to an Antibody Against N‑truncated Abeta in Sporadic Alzheimer Disease Cases and Mouse Models. Acta Neuropathol. 2015;130(5):713-29. PubMed PMID: 26467270.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Abeta targets of the biosimilar antibodies of Bapineuzumab, Crenezumab, Solanezumab in comparison to an antibody against N‑truncated Abeta in sporadic Alzheimer disease cases and mouse models. AU - Bouter,Yvonne, AU - Lopez Noguerola,Jose Socrates, AU - Tucholla,Petra, AU - Crespi,Gabriela A N, AU - Parker,Michael W, AU - Wiltfang,Jens, AU - Miles,Luke A, AU - Bayer,Thomas A, PY - 2015/07/01/received PY - 2015/10/05/accepted PY - 2015/10/05/revised PY - 2015/10/16/entrez PY - 2015/10/16/pubmed PY - 2016/8/12/medline SP - 713 EP - 29 JF - Acta neuropathologica JO - Acta Neuropathol. VL - 130 IS - 5 N2 - Solanezumab and Crenezumab are two humanized antibodies targeting Amyloid-β (Aβ) which are currently tested in multiple clinical trials for the prevention of Alzheimer's disease. However, there is a scientific discussion ongoing about the target engagement of these antibodies. Here, we report the immunohistochemical staining profiles of biosimilar antibodies of Solanezumab, Crenezumab and Bapineuzumab in human formalin-fixed, paraffin-embedded tissue and human fresh frozen tissue. Furthermore, we performed a direct comparative immunohistochemistry analysis of the biosimilar versions of the humanized antibodies in different mouse models including 5XFAD, Tg4-42, TBA42, APP/PS1KI, 3xTg. The staining pattern with these humanized antibodies revealed a surprisingly similar profile. All three antibodies detected plaques, cerebral amyloid angiopathy and intraneuronal Aβ in a similar fashion. Remarkably, Solanezumab showed a strong binding affinity to plaques. We also reaffirmed that Bapineuzumab does not recognize N-truncated or modified Aβ, while Solanezumab and Crenezumab do detect N-terminally modified Aβ peptides Aβ4-42 and pyroglutamate Aβ3-42. In addition, we compared the results with the staining pattern of the mouse NT4X antibody that recognizes specifically Aβ4-42 and pyroglutamate Aβ3-42, but not full-length Aβ1-42. In contrast to the biosimilar antibodies of Solanezumab, Crenezumab and Bapineuzumab, the murine NT4X antibody shows a unique target engagement. NT4X does barely cross-react with amyloid plaques in human tissue. It does, however, detect cerebral amyloid angiopathy in human tissue. In Alzheimer mouse models, NT4X detects intraneuronal Aβ and plaques comparable to the humanized antibodies. In conclusion, the biosimilar antibodies Solanezumab, Crenezumab and Bapineuzumab strongly react with amyloid plaques, which are in contrast to the NT4X antibody that hardly recognizes plaques in human tissue. Therefore, NT4X is the first of a new class of therapeutic antibodies. SN - 1432-0533 UR - https://www.unboundmedicine.com/medline/citation/26467270/Abeta_targets_of_the_biosimilar_antibodies_of_Bapineuzumab_Crenezumab_Solanezumab_in_comparison_to_an_antibody_against_N‑truncated_Abeta_in_sporadic_Alzheimer_disease_cases_and_mouse_models_ L2 - https://dx.doi.org/10.1007/s00401-015-1489-x DB - PRIME DP - Unbound Medicine ER -