Identification of a CEACAM5 targeted nanobody for positron emission tomography imaging and near-infrared fluorescence imaging of colorectal cancer

Xiao, Yitai; Mei, Chaoming; Xu, Duo; Yang, Fan; Yang, Meilin; Bi, Lei; Mao, Junjie; Pang, Pengfei; Li, Dan

doi:10.1007/s00259-023-06183-7

Cited by 8 publications

(5 citation statements)

References 33 publications

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“…Conventional monoclonal antibodies have been exploited to conjugate with fluorescence imaging molecules to obtain tumor selectivity, and realize precise tumor imaging and resection, such as SGM101, a CEA monoclonal antibody conjugated with fluorochrome BM104 for fluorescence-guided surgery to detect CRC and metastasis [ 39 ]. However, full-length monoclonal antibodies with 150 kDa could retain high concentration in the circulation, resulting in a relatively long half-life, low accumulation, and delayed fluorescent peak time in tumor sites, which are unfavorable for use in clinical practical [ 7 , 40 ]. In contrast, Nbs, which are the smallest antibody entities, have been recently given more attention to develop fluorescent probes for surgery navigation owing to their small molecular weight, good tissue penetration, easy preparation with high solubility, and moderate half-life relative to full-length antibodies or tiny peptides.…”

Section: Discussionmentioning

confidence: 99%

Cadherin 17 Nanobody-Mediated Near-Infrared-II Fluorescence Imaging-Guided Surgery and Immunotoxin Delivery for Colorectal Cancer

Ding,

Zhou,

Shi

et al. 2024

Biomater Res

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Surgery and targeted therapy are of equal importance for colorectal cancer (CRC) treatment. However, complete CRC tumor resection remains challenging, and new targeted agents are also needed for efficient CRC treatment. Cadherin 17 (CDH17) is a membrane protein that is highly expressed in CRC and, therefore, is an ideal target for imaging-guided surgery and therapeutics. This study utilizes CDH17 nanobody (E8-Nb) with the near-infrared (NIR) fluorescent dye IRDye800CW to construct a NIR-II fluorescent probe, E8-Nb-IR800CW, and a Pseudomonas exotoxin (PE)-based immunotoxin, E8-Nb-PE38, to evaluate their performance for CRC imaging, imaging-guided precise tumor excision, and antitumor effects. Our results show that E8-Nb-IR800CW efficiently recognizes CDH17 in CRC cells and tumor tissues, produces high-quality NIR-II images for CRC tumors, and enables precise tumor removal guided by NIR-II imaging. Additionally, fluorescent imaging confirms the targeting ability and specificity of the immunotoxin toward CDH17-positive tumors, providing the direct visible evidence for immunotoxin therapy. E8-Nb-PE38 immunotoxin markedly delays the growth of CRC through the induction of apoptosis and immunogenic cell death (ICD) in multiple CRC tumor models. Furthermore, E8-Nb-PE38 combined with 5-FU exerts synergistically antitumor effects and extends survival. This study highlights CDH17 as a promising target for CRC imaging, imaging-guided surgery, and drug delivery. Nanobodies targeting CDH17 hold great potential to construct NIR-II fluorescent probes for surgery navigation, and PE-based toxins fused with CDH17 nanobodies represent a novel therapeutic strategy for CRC treatment. Further investigation is warranted to validate these findings for potential clinical translation.

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Section: Discussionmentioning

confidence: 99%

Cadherin 17 Nanobody-Mediated Near-Infrared-II Fluorescence Imaging-Guided Surgery and Immunotoxin Delivery for Colorectal Cancer

Ding,

Zhou,

Shi

et al. 2024

Biomater Res

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“…One of the most outstanding fields in which VHHs have been applied is diagnosis through imaging [ 46 ]. Single-photon emission computed tomography (SPECT) imaging [ 47 ], near-infrared fluorescence imaging (NIR) [ 48 ], and positron emission tomography (PET) [ 48 ] are all among molecular imaging techniques that have benefited from VHHs because their low rate of unspecific tissue uptake in irrelevant organs results in high target-to-background ratio, which is in sharp contrast with that of the radio-labeled full-length mAbs. VHHs have also been applied as checkpoint blockade therapies, nanobody-drug conjugates, targeted radionuclide therapy, and VHH-based delivery systems [ 41 , 49 – 51 ].…”

Section: Discussionmentioning

confidence: 99%

Characterization of novel CD19-specific VHHs isolated from a camelid immune library by phage display

Ganji,

Safarzadeh Kozani,

Rahbarizadeh

2023

J Transl Med

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Background Monoclonal antibody (mAb)-based immunotherapies have achieved promising outcomes in the treatment of immunological and oncological indications. CD19 is considered one of the most qualified antigens in the treatment of B-cell neoplasms. VHHs (nanobodies) are known for their physicochemical advantages over conventional mAbs rendering them suitable therapeutics and diagnostic tools. Herein, we aimed to isolate CD19-specific VHHs from a novel immune library using phage display. Methods An immune VHH gene library was constructed. Using phage display and after five biopanning rounds, two monoclonal CD19-specific VHHs were isolated. The selected VHHs were expressed, purified, and characterized in terms of their affinity, specificity, sensitivity, and ability to target CD19-positive cell lines. Moreover, in silico analyses were employed for further characterization. Results A VHH library was developed, and because the outputs of the 4th biopanning round exhibited the most favorable characteristics, a panel of random VHHs was selected from them. Ultimately, two of the most favorable VHHs were selected and DNA sequenced (designated as GR37 and GR41). Precise experiments indicated that GR37 and GR41 exhibited considerable specificity, sensitivity, and affinity (1.15 × 107 M−1 and 2.08 × 107 M−1, respectively) to CD19. Flow cytometric analyses revealed that GR37 and GR41 could bind CD19 on the surface of cell lines expressing the antigen. Moreover, in silico experiments predicted that both VHHs target epitopes that are distinct from that targeted by the CD19-specific single-chain variable fragment (scFv) FMC63. Conclusion The selected VHHs can be used as potential targeting tools for the development of CD19-based immunotherapeutics.

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“…In another study focusing on colorectal cancer, similar conclusions were drawn. In this research, a different CEACAM5 nanobody Nb41 was successfully generated and attached to IRDye800CW, resulting in Nb41-IR800, as well as an albumin-binding domain-derived Nb41-ABD-IR800 [77]. Both of these probes exhibited superior imaging capabilities in subcutaneous models, while the latter presented higher fluorescence intensity within the tumor but with a remarkable delay compared to the former.…”

Section: Nanobody-based Near-infrared (Nir) Optical Imagingmentioning

confidence: 99%

Small Antibodies with Big Applications: Nanobody-Based Cancer Diagnostics and Therapeutics

Zhang,

Xiao

et al. 2023

Cancers

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Monoclonal antibodies (mAbs) have exhibited substantial potential as targeted therapeutics in cancer treatment due to their precise antigen-binding specificity. Despite their success in tumor-targeted therapies, their effectiveness is hindered by their large size and limited tissue permeability. Camelid-derived single-domain antibodies, also known as nanobodies, represent the smallest naturally occurring antibody fragments. Nanobodies offer distinct advantages over traditional mAbs, including their smaller size, high stability, lower manufacturing costs, and deeper tissue penetration capabilities. They have demonstrated significant roles as both diagnostic and therapeutic tools in cancer research and are also considered as the next generation of antibody drugs. In this review, our objective is to provide readers with insights into the development and various applications of nanobodies in the field of cancer treatment, along with an exploration of the challenges and strategies for their prospective clinical trials.

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Identification of a CEACAM5 targeted nanobody for positron emission tomography imaging and near-infrared fluorescence imaging of colorectal cancer

Cited by 8 publications

References 33 publications

Cadherin 17 Nanobody-Mediated Near-Infrared-II Fluorescence Imaging-Guided Surgery and Immunotoxin Delivery for Colorectal Cancer

Cadherin 17 Nanobody-Mediated Near-Infrared-II Fluorescence Imaging-Guided Surgery and Immunotoxin Delivery for Colorectal Cancer

Characterization of novel CD19-specific VHHs isolated from a camelid immune library by phage display

Small Antibodies with Big Applications: Nanobody-Based Cancer Diagnostics and Therapeutics

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