Evaluation of COC183B2 antibody targeting ovarian cancer by near-infrared fluorescence imaging

Zhang, Chen; Ling, Xinyu; Guo, Yanxiu; Yuan, Cunzhong; Cheng, Hongyan; Xue, Yu; Ma, Ruiqiong; Zhang, Yinli; Li, Yang; Chang, Xiaohong; Kong, Beihua; Liu, Tao; Cui, Heng

doi:10.21147/j.issn.1000-9604.2019.04.11

Cited by 10 publications

(10 citation statements)

References 31 publications

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“…However, antibodies conjugated with USPIOs might be toxic. Cy7 has not been approved for use in humans, and our previous work showed the phenomenon of lung accumulation of Cy7-conjugated COC183B2 [10]. As previously described, IRDye800CW is a safe and effective NIRF dye.…”

Section: Discussionmentioning

confidence: 73%

“…Moreover, the lesions of patients are not visible during the operation due to the imaging modality. We later conjugated ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) and Cy7 with COC183B2 antibody and achieved early detection of EOC through OC183B2targeted MRI and fluorescence imaging [10,25]. However, antibodies conjugated with USPIOs might be toxic.…”

Section: Discussionmentioning

confidence: 99%

“…Immunohistochemistry (IHC) staining of EOC tissues IHC staining was conducted in the human EOC tissues of 69 patients using COC183B2 antibody as previously described [10]. Mouse immunoglobulin G1 (IgG1) (Cat# ab81032, Abcam, USA) was used as the negative control.…”

Section: Methodsmentioning

confidence: 99%

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Evaluation of a novel ovarian cancer-specific fluorescent antibody probe for targeted near-infrared fluorescence imaging

et al. 2020

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Background: To meet clinical needs, fluorescence-guided surgery has emerged as a new technique that guides surgeons in the resection of cancerous tissue by highlighting tumour lesions during surgery. We aimed to evaluate the novel ovarian cancer-specific antibody fluorescent probe COC183B2-800 (COC183B2 conjugated with IRDye800CW) in tumour-specific imaging to determine if it can help surgeons remove malignant lesions under fluorescence guidance. Methods: The expression of OC183B2 antigen in epithelial ovarian cancer (EOC) tissues and cell lines was determined using immunohistochemistry (IHC). Western blotting was used to verify the expression of OC183B2 in SKOV3-Luc tumours. Antibodies against OC183B2 and mouse immunoglobulin G1 (IgG1) were conjugated with IRDye800CW to develop the antibody fluorescent probes COC183B2-800 and IgG-800 (immunoglobulin G1 conjugated with IRDye800CW). A subcutaneous mouse tumour model of SKOV3-Luc cells was constructed. Bioluminescent imaging (BLI) was conducted to detect the tumour location. Near-infrared fluorescence (NIRF) imaging was performed after the mice were injected with imaging agents. The mice were sacrificed 96 h postinjection, and the biodistribution assays were performed using NIRF imaging. Results: In 69 EOC patients, the total positive rate of OC183B2 in EOC tissues was 89.9% (62/69). Expression of the OC183B2 antigen was positive in SKOV3-Luc, 3AO, ES2 and A2780 cells. The OC183B2 antigen could be detected in SKOV3-Luc tumours. NIRF imaging of the COC183B2-800 probe at different doses showed a high fluorescent signal at the tumour location that was in line with the site detected by bioluminescent imaging. The tumour background ratio (TBR) was significantly higher in the COC183B2-800 group than in the IgG-800, IRDye800CW and PBS groups. The fluorescent probe COC183B2-800 is metabolized mainly through the liver and does not accumulate in other organs.Conclusions: COC183B2-800 shows effective tumour-specific targeting of EOC and is a promising diagnostic and therapeutic tool for fluorescence-guided surgery.

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Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

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Evaluation of a novel ovarian cancer-specific fluorescent antibody probe for targeted near-infrared fluorescence imaging

et al. 2020

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“…Of note, it has repeatedly been suggested that patients responding immunologically to DC therapy have better outcomes. [12][13][14][15] This finding could indicate that immune competent patients have better outcomes than highly immune suppressed patients, [16][17][18] without DCs necessarily playing a role. An interesting outlier to lack of randomized efficacy is sipuleucel T, which is a mixed product containing T cells and DCs.…”

Section: Introductionmentioning

confidence: 99%

CD40L coding oncolytic adenovirus allows long-term survival of humanized mice receiving dendritic cell therapy

et al. 2018

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Dendritic cells (DCs) are crucial players in promoting immune responses. Logically, adoptive DC therapy is a promising approach in cancer immunotherapy. One of the major obstacles in cancer immunotherapy in general is the immunosuppressive tumor microenvironment, which hampers the maturation and activation of DCs. Therefore, human clinical outcomes with DC therapy alone have been disappointing. In this study, we use fully serotype 3 oncolytic adenovirus Ad3-hTERT-CMV-hCD40L, expressing human CD40L, to modulate the tumor microenvironment with subsequently improved function of DCs. We evaluated the synergistic effects of Ad3-hTERT-CMV-hCD40L and DCs in the presence of human peripheral blood mononuclear cells ex vivo and in vivo. Tumors treated with Ad3-hTERT-CMV-hCD40L and DCs featured greater antitumor effect compared with unarmed virus or either treatment alone. 100% of humanized mice survived to the end of the experiment, while mice in all other groups died by day 88. Moreover, adenovirally-delivered CD40L induced activation of DCs, leading to induction of Th1 immune responses. These results support clinical trials with Ad3-hTERT-CMV-hCD40L in patients receiving DC therapy.

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“…We proved the tumor-specific imaging ability of COC183B2-Cy7 in tumor tissue from a mouse model. 16 However, it remains unclear whether COC183B2-Cy7 can detect metastatic lymph nodes, and its specific in vivo biodistribution and ability to identify tiny metastatic lesions remain unknown. Therefore, we aimed to detect OC183B2 expression in metastatic lymph nodes and to determine the imaging parameters of COC183B2-Cy7 in a mouse subcutaneous tumor model.…”

mentioning

confidence: 99%

Near‐infrared dye‐labeled antibody COC183B2 enables detection of tiny metastatic ovarian cancer and optimizes fluorescence‐guided surgery

Chen

Guo

et al. 2020

Journal of Surgical Oncology

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Objective: We aimed to evaluate the ability of the fluorescent monoclonal antibody probe COC183B2-Cy7 (Cy7-conjugated COC183B2 antibody) to detect tiny metastatic lesions of ovarian cancer and thus guide precise tumor resection. Methods: The expression of the tumor-associated antigen OC183B2 in lymph nodes and SKOV3-Luc cells was detected using immunohistochemistry and immunofluorescence. A subcutaneous mouse tumor model and an intraperitoneal ovarian cancer metastasis model were constructed using SKOV3-Luc cells. Near-infrared fluorescence (NIRF) imaging was performed to determine the imaging parameters and evaluate the ability of COC183B2-Cy7 to detect tiny metastatic lesions. Results: OC183B2 was expressed in metastatic lymph nodes and SKOV3-Luc cells. NIRF imaging of the subcutaneous mouse tumor model showed that the tumor background ratio was significantly higher in the COC183B2-Cy7 group than in the control group at different time points postinjection. Biodistribution study showed that COC183B2-Cy7 did not accumulate in other organs. COC183B2-Cy7 can detect tiny metastatic lesions of ovarian cancer. The smallest intraperitoneal metastatic tumor detected by COC183B2-Cy7 was approximately 1 mm. Conclusions: COC183B2-Cy7 probe has relatively high specificity and sensitivity. Our study suggests that COC183B2-Cy7 probe is a promising diagnostic tool for the complete and accurate resection of malignant lesions in fluorescence-guided surgery.

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Evaluation of COC183B2 antibody targeting ovarian cancer by near-infrared fluorescence imaging

Cited by 10 publications

References 31 publications

Evaluation of a novel ovarian cancer-specific fluorescent antibody probe for targeted near-infrared fluorescence imaging

Evaluation of a novel ovarian cancer-specific fluorescent antibody probe for targeted near-infrared fluorescence imaging

CD40L coding oncolytic adenovirus allows long-term survival of humanized mice receiving dendritic cell therapy

Near‐infrared dye‐labeled antibody COC183B2 enables detection of tiny metastatic ovarian cancer and optimizes fluorescence‐guided surgery

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