Generation and characterization of LPA-KIV9, a murine monoclonal antibody binding a single site on apolipoprotein (a)

Bibliographic Details
Title: Generation and characterization of LPA-KIV9, a murine monoclonal antibody binding a single site on apolipoprotein (a)
Authors: Ayelet Gonen, Xiaohong Yang, Calvin Yeang, Elena Alekseeva, Marlys Koschinsky, Joseph L. Witztum, Michael Boffa, Sotirios Tsimikas
Source: Journal of Lipid Research, Vol 61, Iss 9, Pp 1263-1270 (2020)
Publisher Information: Elsevier, 2020.
Publication Year: 2020
Collection: LCC:Biochemistry
Subject Terms: lipoprotein (a), monoclonal antibody, isoform, kringle, cardiovascular disease, aortic stenosis, Biochemistry, QD415-436
More Details: Lipoprotein (a) [Lp(a)] is a risk factor for CVD and a target of therapy, but Lp(a) measurements are not globally standardized. Commercially available assays generally use polyclonal antibodies that detect multiple sites within the kringle (K)IV2 repeat region of Lp(a) and may lead to inaccurate assessments of plasma levels. With increasing awareness of Lp(a) as a cardiovascular risk factor and the active clinical development of new potential therapeutic approaches, the broad availability of reagents capable of providing isoform independence of Lp(a) measurements is paramount. To address this issue, we generated a murine monoclonal antibody that binds to only one site on apo(a). A BALB/C mouse was immunized with a truncated version of apo(a) that contained eight total KIV repeats, including only one copy of KIV2. We generated hybridomas, screened them, and successfully produced a KIV2-independent monoclonal antibody, named LPA-KIV9. Using a variety of truncated apo(a) constructs to map its binding site, we found that LPA-KIV9 binds to KIV9 without binding to plasminogen. Fine peptide mapping revealed that LPA-KIV9 bound to the sequence 4076LETPTVV4082 on KIV9. In conclusion, the generation of monoclonal antibody LPA-KIV9 may be a useful reagent in basic research studies and in the clinical application of Lp(a) measurements.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 0022-2275
Relation: http://www.sciencedirect.com/science/article/pii/S0022227520436910; https://doaj.org/toc/0022-2275
DOI: 10.1194/jlr.RA120000830
Access URL: https://doaj.org/article/d3ae9551f9854ddb99fa732ebadefc2a
Accession Number: edsdoj.3ae9551f9854ddb99fa732ebadefc2a
Database: Directory of Open Access Journals
More Details
ISSN:00222275
DOI:10.1194/jlr.RA120000830
Published in:Journal of Lipid Research
Language:English