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Investigation of Antibody-Drug Conjugates by Mass Spectrometry

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Advancements of Mass Spectrometry in Biomedical Research

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1140))

Abstract

ADCs are empowered monoclonal antibodies that are designed to harness their targeting ability by linking them to cell-killing agents. They are made up of three main components, the antibody, linker and the cytotoxic drug. The specificity of the antibody with the antigen on the tumor cell surface helps with its internalization into the cell after which the active drug is released causing cell death. The investigation of ADCs can be done using a variety of MS methods. Here, we talk about the bottom-up approach, the top-down approaches such as ECD and ETD, the ESI/MS method and IM-MS. Further, we also focus on the applications of MALDI/MS such as UV-MALDI, IR-MALDI and IMS-MALDI and provide examples of the mass spectra that provide tremendous amount of information on ADC structures.

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Abbreviations

ADC:

Antibody-drug conjugates

ALCL:

Anaplastic large cell lymphoma

CDRs:

Complementary determining regions

DAR:

Drug to antibody ratio

ECD:

Electron capture dissociation

ESI:

Electrospray ionization

ETD:

Electron transfer dissociation

HL:

Hodgkin’s lymphoma

IM:

Ion mobility

mAbs:

Monoclonal antibodies

MALDI:

Matrix assisted laser desorption ionization

MMAE:

Monomethyl auristatin E

MS:

Mass spectrometry

PTM:

Posttranslational modification

SCLC:

Small cell lung carcinoma

TDCs:

THIOMAB drug conjugates

TOF:

Time of flight

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Acknowledgements

We would like to thank the past and current lab members for creating a pleasant working environment.

Author information

Authors and Affiliations

  1. Biochemistry and Proteomics Group, Department of Chemistry and Biomolecular Science, Clarkson University, Potsdam, NY, USA

    Madhuri Jayathirtha & Costel C. Darie

Authors
  1. Madhuri Jayathirtha
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  2. Costel C. Darie
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Corresponding author

Correspondence to Costel C. Darie .

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Editors and Affiliations

  1. Biochemistry and Proteomics Group, Department of Chemistry and Biomolecular Science, Clarkson University, Potsdam, NY, USA

    Alisa G. Woods

  2. Biochemistry and Proteomics Group, Department of Chemistry and Biomolecular Science, Clarkson University, Potsdam, NY, USA

    Costel C. Darie

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Jayathirtha, M., Darie, C.C. (2019). Investigation of Antibody-Drug Conjugates by Mass Spectrometry. In: Woods, A., Darie, C. (eds) Advancements of Mass Spectrometry in Biomedical Research. Advances in Experimental Medicine and Biology, vol 1140. Springer, Cham. https://doi.org/10.1007/978-3-030-15950-4_14

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