Oncotarget

Research Papers:

Tissue biodistribution and tumor targeting of near-infrared labelled anti-CD38 antibody-drug conjugate in preclinical multiple myeloma

Nicholas Cho, Sooah Ko and Monica Shokeen _

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Oncotarget. 2021; 12:2039-2050. https://doi.org/10.18632/oncotarget.28074

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Abstract

Nicholas Cho1,2, Sooah Ko2 and Monica Shokeen1,2,3

1 Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA

2 Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, USA

3 Alvin J. Siteman Cancer Center, Washington University School of Medicine and Barnes-Jewish Hospital, St. Louis, MO, USA

Correspondence to:

Monica Shokeen, email: shokeenm@wustl.edu

Keywords: near-infrared (NIR) fluorescence; multiple myeloma (MM); cluster of differentiation 38 (CD38); antibody-drug conjugate (ADC); small animal optical imaging

Received: July 12, 2021     Accepted: August 18, 2021     Published: September 28, 2021

Copyright: © 2021 Cho et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Daratumumab (DARA) is an FDA-approved high-affinity monoclonal antibody targeting CD38 that has shown promising therapeutic efficacy in double refractory multiple myeloma (MM) patients. Despite the well-established clinical efficacy of DARA, not all heavily pretreated patients respond to single-agent DARA, and the majority of patients who initially respond eventually progress. Antibody-drug conjugates (ADCs) combine the highly targeted tumor antigen recognition of antibodies with the cell killing properties of chemotherapy for effective internalization and processing of the drug. In this study, we evaluated the anti-tumor efficacy of DARA conjugated to the maytansine derivative, mertansine (DM1), linked via a non-cleavable bifunctional linker. The ADC was labelled with the near-infrared (NIR) fluorophore IRDye800 (DARA-DM1-IR) to evaluate its stability, biodistribution and pharmacokinetics in vitro and in vivo. We demonstrated the conjugation of: 1) DM1 enhanced tumor-killing efficacy of the native DARA and 2) IRDye800 allowed for visualization of uptake and tumor targeting ability of the ADC. With the advent of other classes of immunoconjugates for use in MM, we reasoned that such imaging techniques can be utilized to evaluate other promising conjugates in preclinical MM models on a whole-body and cellular level.


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