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J Pharm Biomed Anal. 2016 Nov 30;131:309-315. doi: 10.1016/j.jpba.2016.09.009. Epub 2016 Sep 5.

Development, validation, and application of ELISA for detection of anti-HD105 antibodies in pre-clinical safety evaluation using monkeys.

Author information

1
College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea; Korea Institute of Toxicology, 141 Gajeong-ro, Yuseong-gu, Daejeon, Republic of Korea.
2
Korea Institute of Toxicology, 141 Gajeong-ro, Yuseong-gu, Daejeon, Republic of Korea.
3
College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
4
Hanwha Chemical R&D Center, Biologics Business Unit, Gajeong-Ro, Yuseong-Gu, Daejeon, Republic of Korea.
5
College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea. Electronic address: sangkim@cnu.ac.kr.

Abstract

Unwanted immunogenicity of protein therapeutics can result in severe side effects and should be assessed in animals before applying the treatment to humans. Monkeys are the most relevant choice for pre-clinical toxicity testing of antibody-based therapeutics. To assess the immunogenicity of HD105, a novel antibody therapeutic that targets both vascular endothelial growth factor and Delta-like-ligand 4, a bridging enzyme-linked immunosorbent assay was developed as an anti-drug antibody (ADA) assay and validated for use in pre-clinical studies using non-human primates. This method was found to have suitable assay sensitivity, intra- and inter-assay precision, confirmation, drug tolerance, recovery, and sample stability for measuring ADA in monkey serum samples. The results showed that ADA elevation occurred following repeated doses of HD105, and that ADA production was negatively associated with serum HD105 concentration. These results suggest that intravenous administration of HD105 induces production of ADA in monkeys and that the detection of ADA may be negatively influenced by free HD105 in serum.

KEYWORDS:

Anti-drug antibody; Bispecific antibody; Immunogenicity; Preclinical study; Therapeutic proteins; Validation

PMID:
27619177
DOI:
10.1016/j.jpba.2016.09.009
[Indexed for MEDLINE]

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