Analytical and bioanalytical technologies for characterizing antibody–drug conjugates

Alley, Stephen C.; Anderson, Kenneth N.

doi:10.1016/j.cbpa.2013.03.022

Cited by 48 publications

(22 citation statements)

References 31 publications

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“…characterization of ADCs have also been reviewed recently. 57,58 As ADCs are very complex molecules, it is usually necessary to examine a particular aspect of stability by two or more techniques using an appropriate experimental design. In general, physical stability has been examined by solution spectroscopic techniques in Table 1 such as circular dichroism, UV-Vis, fluorescence, or dynamic light scattering.…”

Section: Experimental Methods For Adc Stability Analysismentioning

confidence: 99%

Physical and Chemical Stability of Antibody Drug Conjugates: Current Status

Ross¹,

Wolfe²

2016

Journal of Pharmaceutical Sciences

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Antibody drug conjugates (ADCs) are an emerging class of chemotherapeutic cancer treatment agents that combine the targeting specificity of antibodies with the efficient cell-killing potential of cytotoxic drugs. Unlike their protein and small-molecule therapeutic counterparts, the stability and degradation properties of ADCs are relatively unknown. Theoretically, ADC stability could be governed by properties and processes stemming from both the antibody and the linker-toxin chemistry. Recently, systematic studies of intrinsic ADC molecule stability have been presented in the primary literature. As there are burgeoning industrial and academic efforts aimed at developing optimized conjugation chemistries and antibody engineering approaches for next-generation ADCs, it is important to capture the current state of understanding of ADC stability. In this minireview, we discuss aspects of physical and chemical stability of ADCs gathered from a survey of the literature and illustrate how investigations into stability enable the development of more effective ADC molecules for the future.

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Section: Experimental Methods For Adc Stability Analysismentioning

confidence: 99%

Physical and Chemical Stability of Antibody Drug Conjugates: Current Status

Ross¹,

Wolfe²

2016

Journal of Pharmaceutical Sciences

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“…The Cartesian coordinates of an atom of a molecule correspond to the variables x,y,z, x′,y′,z′ of Eqs. (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). The scaling factor α was always set to the value of 1, because scaling the molecules would result in the disruption of their structure.…”

Section: Affine Transformationmentioning

confidence: 99%

“…Considering the conjugation of two molecules per antibody as 100% conjugation efficiency, most THIOMABs demonstrated more than 90% conjugation efficiency, proving to be suitable for site-specific conjugation of thiol reactive probes. THIOMAB-drug conjugates (TDCs) are the product of the conjugation of a drug to a THIOMAB [11,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

A Bioinformatics Method for the Production of Antibody-Drug Conjugates Through Site-Specific Cysteine Conjugation

Filntisi¹,

Vlachakis²,

Matsopoulos³

2016

Bioinformatics - Updated Features and Applications

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Antibody-drug conjugates (ADCs) have emerged as a promising class of targeted anticancer therapy, and it is distinguished from traditional chemotherapeutic approaches by its potential to kill cancer cells with limited side effects. Site-specific conjugation is one of the current challenges in ADC development because it allows for controlled conjugation and production of homogeneous ADCs. This chapter describes a computational method for the generation of antibody-drug conjugates as PDB files through site-specific cysteine conjugation, given the PDB files of a drug, a linker, and an antibody. The drug and linker are reconfigured using the rotation and translation functions of an affine transformation, which is brought in appropriate positions for the bonds to occur between the three molecules. The hydrogen and disulfide bonds are employed to connect the linker and drug as well as the linker with the antibody, respectively. Examples of conjugates produced with the presented method have been demonstrated.

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“…Pharmacokinetic studies have shown that an average of four drugs per antibody binding site produces a stable compound that effectively delivers optimal drug concentrations into malignant cells that express the target antigens (33, 34). More heavily loaded drug concentrations tend to be rapidly cleared from the circulation or cause aggregation and impair antigen binding (12).…”

Section: Conjugated Monoclonal Antibodiesmentioning

confidence: 99%

Antibody Therapy for Pediatric Leukemia

Vedi

Ziegler

2014

Front. Oncol.

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Despite increasing cure rates for pediatric leukemia, relapsed disease still carries a poor prognosis with significant morbidity and mortality. Novel targeted therapies are currently being investigated in an attempt to reduce adverse events and improve survival outcomes. Antibody therapies represent a form of targeted therapy that offers a new treatment paradigm. Monoclonal antibodies are active in pediatric acute lymphoblastic leukemia (ALL) and are currently in Phase III trials. Antibody-drug conjugates (ADCs) are the next generation of antibodies where a highly potent cytotoxic agent is bound to an antibody by a linker, resulting in selective targeting of leukemia cells. ADCs are currently being tested in clinical trials for pediatric acute myeloid leukemia and ALL. Bispecific T cell engager (BiTE) antibodies are a construct whereby each antibody contains two binding sites, with one designed to engage the patient’s own immune system and the other to target malignant cells. BiTE antibodies show great promise as a novel and effective therapy for childhood leukemia. This review will outline recent developments in targeted agents for pediatric leukemia including monoclonal antibodies, ADCs, and BiTE antibodies.

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Analytical and bioanalytical technologies for characterizing antibody–drug conjugates

Cited by 48 publications

References 31 publications

Physical and Chemical Stability of Antibody Drug Conjugates: Current Status

Physical and Chemical Stability of Antibody Drug Conjugates: Current Status

A Bioinformatics Method for the Production of Antibody-Drug Conjugates Through Site-Specific Cysteine Conjugation

Antibody Therapy for Pediatric Leukemia

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