Improved resection and prolonged overall survival with PD-1-IRDye800CW fluorescence probe-guided surgery and PD-1 adjuvant immunotherapy in 4T1 mouse model

Abstract

An intraoperative technique to accurately identify microscopic tumor residuals could decrease the risk of positive surgical margins. Several lines of evidence support the expression and immunotherapeutic effect of PD-1 in breast cancer. Here, we sought to develop a fluorescence-labeled PD-1 probe for in vivo breast tumor imaging and image-guided surgery. The efficacy of PD-1 monoclonal antibody (PD-1 mAb) as adjuvant immunotherapy after surgery was also assessed. PD-1-IRDye800CW was developed and examined for its application in tumor imaging and image-guided tumor resection in an immunocompetent 4T1 mouse tumor model. Fluorescence molecular imaging was performed to monitor probe biodistribution and intraoperative imaging. Bioluminescence imaging was performed to monitor tumor growth and evaluate postsurgical tumor residuals, recurrences, and metastases. The PD-1-IRDye800CW exhibited a specific signal at the tumor region compared with the IgG control. Furthermore, PD-1-IRDye800CW-guided surgery combined with PD-1 adjuvant immunotherapy inhibited tumor regrowth and microtumor metastases and thus improved survival rate. Our study demonstrates the feasibility of using PD-1-IRDye800CW for breast tumor imaging and image-guided tumor resection. Moreover, PD-1 mAb adjuvant immunotherapy reduces cancer recurrences and metastases emanating from tumor residuals.

Noninvasive imaging of the PD-1:PD-L1 immune checkpoint: Embracing nuclear medicine for the benefit of personalized immunotherapy

“…They also observed that tumor growth was significantly inhibited in the PD-1-Liposome-DOX-treated group than the IgG control. More recently, the same group published a study that demonstrates the feasibility of using the same PD-1-IRDye800CW-conjugated liposomes for image-guided tumor resection 62 , 63 .…”

Development of Radiotracers for Imaging of the PD-1/PD-L1 Axis

“…[24] mAb PD-1-IRDye800CW IRDye800CW NIRF n.a. [25] PD-1/PD-L1 mAb NOTA-α-PD-1 (RMP1-14) NOTA-α-PD-L1 (10F.9G2) 64 Cu PET n.a. [26] mAb Adnectin Df-Nivolumab BMS-986192 89 Zr [ 18 F]AlF PET n.a.…”

<p>Application and Prospects of Molecular Imaging in Immunotherapy</p>

“…The result further demonstrated the feasibility that using PD-1-IRDye800CW to detect PD-L1 expression by fluorescence optical imaging. 60 PAI is usually used for local tissue imaging due to the higher resolution and tissue penetration depth. Liposome-based probes for PAI had be proven the feasibility to guide image tumors.…”