Multiplexed Serum Measurement of IgG, IgA, IgM, and IgE Antibody Responses to Therapeutic Biologicals

McCutcheon, Krista; O'Hara, Edward T.; Fei, David

doi:10.1081/imm-200055820

Cited by 3 publications

(2 citation statements)

References 2 publications

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“…Serum IgG, IgA and IgM are the molecular basis of humoral immune responsesplaying a role in specific immunity responses. In addition, IgG and IgM can activate the classical pathway of complement to take part in non-specific immunity responses 25 .…”

Section: Mass Spectrometry (Esi-ms)mentioning

confidence: 99%

Preparation and Immunological Evaluation of Organic Acid Salts of Levamisole

Xu¹,

Yang²,

Wang³

2014

Asian J. Chem.

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Levamisole (LMS), the levo-isomer of tetramisole, is an anthelminthic belonging to a class of synthetic imidazothiazole derivatives, as well as an immunomodulator which can enhance the immune responses [1][2][3][4][5] . Due to the poor solubility and instability in water, its hydrochloride (levamisole hydrochloride, LH) is commonly used in clinical. However, LH still has problems of low bioavailability and side effects, such as a certain stimulus to the human body. In the past decade, a large number of researches have been increasingly reported with respect to chemical modifications of drugs, such as esterification 6 , acylation 7 , amidation 8 , alkylation 9 , anhydride formation 10 , salt formation [11][12][13][14][15][16][17] , ring opening and formation 18,19 . As reported, chemical modifications have many advantages such as improving the solubility, stability and bioavailability of drugs, reducing toxic reactions, enhancing pharmacological effects, extending drug action, making other drug dosage forms and delivery systems possible or more excellent, etc.Salt formation is a simple and effective chemical modification, which can influence a number of physicochemical properties of the parent drug, including solubility, dissolution rate, stability and hygroscopicity 11 . As a result, different salts of drugs may bring about different pharmacokinetic and pharmacodynamic qualities and therefore different clinical qualities; some even may show intrinsic toxicity 14 . Levamisole base has a tertiary nitrogen atom, whose lone pair of electrons can accept

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Section: Mass Spectrometry (Esi-ms)mentioning

confidence: 99%

Preparation and Immunological Evaluation of Organic Acid Salts of Levamisole

Xu¹,

Yang²,

Wang³

2014

Asian J. Chem.

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“…McCutcheon et al . developed a multiplexed ADA isotyping assay in cynomolgus monkeys treated with Raptiva (humanized monoclonal antibody to CD11a) ( 15 ). The study showed the ability to measure IgG, IgM, IgA, and IgE ADA antibodies in a single assay format.…”

Section: Introductionmentioning

confidence: 99%

Design and Evaluation of a Multiplexed Assay to Assess Human Immunogenicity Against Humira®

Alleyn¹,

Closson²,

Gentile³

et al. 2020

AAPS J

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The use of biologic-based therapeutics has revolutionized our ability to treat complex diseases such as cancer- and autoimmune-related disorders. Biologic-based therapeutics are known to generate anti-drug immune responses or immunogenicity in clinical patients which can lead to altered pharmacokinetics, decreased drug efficacy, and unwanted adverse clinical events. Assays designed to detect and assess anti-drug immune responses are used to help monitor patients and improve drug safety. Utilizing a tiered approach, screening assays are developed first to identify patients that are potentially positive for anti-drug-specific antibodies. Patients that screen positive are subjected to additional tiers of testing that include a confirmation assay to confirm the presence of expected anti-drug-specific antibodies, a titer assay to assess relative levels of anti-drug-specific antibodies, and, depending on the drug’s mechanism of action or concerns of adverse clinical reactions, further characterization such as drug neutralization and anti-drug antibody isotyping. This tiered approach can prove to be detrimental to clinical samples from exposure to multiple cycles of testing, freeze thaws, and repeated handling by lab personnel. Multiplexing some of these assays together may streamline the characterization of anti-drug immune responses and help reduce the repeated usage of clinical samples. In this study, we combined a screening assay and anti-drug isotyping assays into one multiplexed assay using the Luminex® xMAP® Technology. The multiplexed assay was developed and validated to meet the FDA recommended guidelines for immunogenicity assessments. These results show that multiplexed assays perform comparably to industry standards. This study should encourage labs to explore the use of multiplexing immunogenicity assays to characterize anti-drug antibody responses quickly, with less repeat testing and reduced sample handling.

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