Tissue biodistribution and tumor targeting of near-infrared labelled anti-CD38 antibody-drug conjugate in preclinical multiple myeloma
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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
|Monica Shokeen,||email:||[email protected]|
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
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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