Development of a humanized anti-CEA antibody for fluorescent guided surgery of GI cancers

Paul J. Yazaki; Thinzar M. Lwin; Megan Minnix; Lin Li; Anakim Sherman; Justin Molnar; Aaron Miller; Junie Chea; Erasmus Poku; Nicole Bowles; Robert Hoffman; John E. Shively; Michael Bouvet

doi:10.1117/12.2511771

7 March 2019 Development of a humanized anti-CEA antibody for fluorescent guided surgery of GI cancers

Paul J. Yazaki, Thinzar M. Lwin, Megan Minnix , Lin Li, Anakim Sherman, Justin Molnar, Aaron Miller, Junie Chea, Erasmus Poku, Nicole Bowles, Robert Hoffman, John E. Shively, Michael Bouvet

Author Affiliations +

Proceedings Volume 10862, Molecular-Guided Surgery: Molecules, Devices, and Applications V; 108620N (2019) https://doi.org/10.1117/12.2511771
Event: SPIE BiOS, 2019, San Francisco, California, United States

Abstract

In proof-of-concept studies, the anti-CEA M5A-IR800 conjugate demonstrated rapid and effective near infrared (NIR) imaging of human colon cancer and pancreatic cancer primary and metastatic lesions in mouse models. A limitation observed from these studies is the antibody-dye conjugate’s rapid clearance from the blood due to the increased hydrophobicity of the IR800 dye. This is a bottleneck for clinical applications, requiring high doses to be administered and a short surgical time window for intraoperative imaging. As a result, we developed a new prototype anti-CEA-swPEG-IR800 conjugate, that incorporates a PEGylated sidearm linker to shield or mask the IR800 dye’s hydrophobicity, a novel approach to extend the blood circulation half-life and in doing so increase tumor sensitivity as well as lower normal hepatic uptake. Results of the anti-CEA-swPEG-IR800 in an orthotopic human pancreatic cancer mouse model demonstrated exceptional optical imaging at lower doses, a much longer in vivo half-life enabling increased tumor fluorescence and higher tumor to background ratios. We propose that our novel anti-CEA-swPEG-IR800 is capable of enhanced optical imaging than currently available agents and will become the next generation optical imaging agent for safe and effective intraoperative image-guided surgery in CEA expressing GI cancers.

Conference Presentation

Citation Download Citation

Paul J. Yazaki, Thinzar M. Lwin, Megan Minnix , Lin Li, Anakim Sherman, Justin Molnar, Aaron Miller, Junie Chea, Erasmus Poku, Nicole Bowles, Robert Hoffman, John E. Shively, and Michael Bouvet "Development of a humanized anti-CEA antibody for fluorescent guided surgery of GI cancers", Proc. SPIE 10862, Molecular-Guided Surgery: Molecules, Devices, and Applications V, 108620N (7 March 2019); https://doi.org/10.1117/12.2511771

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