In vitro and in vivo application of anti-cotinine antibody and cotinine-conjugated compounds

Abstract

The combination of a high-affinity antibody to a hapten, and hapten-conjugated compounds, can provide an alternative to the direct chemical cross-linking of the antibody and compounds. An optimal hapten for in vitro use is one that is absent in biological systems. For in vivo applications, additional characteristics such as pharmacological safety and physiological inertness would be beneficial. Additionally, methods for cross-linking the hapten to various chemical compounds should be available. Cotinine, a major metabolite of nicotine, is considered advantageous in these aspects. A high-affinity anti-cotinine recombinant antibody has recently become available, and can be converted into various formats, including a bispecific antibody. The bispecific anti-cotinine antibody was successfully applied to immunoblot, enzyme immunoassay, immunoaffinity purification, and pre-targeted in vivo radioimmunoimaging. The anti-cotinine IgG molecule could be complexed with aptamers to form a novel affinity unit, and extended the in vivo half-life of aptamers, opening up the possibility of applying the same strategy to therapeutic peptides and chemical compounds. [BMB Reports 2014; 47(3): 130-134]

Chicken scFvs with an Artificial Cysteine for Site-Directed Conjugation

“…Antibody-drug conjugates (ADCs) have recently become available for the treatment of cancers. Two ADCs, trastuzumab emtansine (T-DM1, Kadcyla) and brentuximab vedotin (Adcetris), have been approved for the treatment of human epidermal growth factor receptor-2 (HER2)-positive metastatic and recurrent breast cancer and lymphoma, respectively [ 3 ].…”

An anti-EGFR × cotinine bispecific antibody complexed with cotinine-conjugated duocarmycin inhibits growth of EGFR-positive cancer cells with KRAS mutations

“…We previously reviewed important factors to consider in selecting a hapten either to be conjugated with an aptamer or isotope-conjugated peptide to extend the in vivo half-life of the aptamer or peptide to be complexed with an antibody for in vivo imaging 18 , 20 , 33 , 44 , 45 . For these purposes, an optimal hapten should be absent from biological systems, and its pharmacological safety and physiological inertness are essential.…”

“…Histamine-succinyl-glycine, diethylenetriamine pentaacetic acid (DTPA), and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) have been classically used 46 – 48 . Recently, we proposed cotinine as an ideal hapten 45 . It is a small chemical with a molecular weight of 176.22 and is a major metabolite of nicotine.…”

“…However, for the purpose of developing an antibody conjugated with cytotoxic agents, a compound with some toxicity might be more beneficial. A high-affinity anti-cotinine antibody was originally generated by our group with k on , k off , and K D values of 2.6×10 6 M − 1 × s −1 , 1.3×10 −5 s −1 , and 4.9×10 − 12 M, respectively 45 . This antibody binds specifically to cotinine and does not cross-react with chemicals with similar structures, such as nicotine, anabasine, caffeine, or cholesterol.…”

A modifiable universal cotinine-chimeric antigen system of NK cells with multiple targets

“…Cotinine(Cot), a major metabolite of nicotine, is a small molecule with a molecular weight of 176.22 and is a hapten, which means it can only elicit an immune response when conjugated with a carrier protein. A daily dose of up to 1,800 mg of cotinine for four consecutive days demonstrated no deleterious side effects (18). The carboxyl group of carboxycotinine (trans-4-cotinincarboxylic acid) can be chemically crosslinked with an affibody or antibody (18), such as trastuzumab, cetuximab, and rituximab, which are clinically used to target TAAs.…”