Endoscopic molecular imaging of human bladder cancer using a CD47 antibody

Pan, Yuxin; Volkmer, Jens Peter; Mach, Kathleen E.; Rouse, Robert V.; Liu, Jen Jane; Sahoo, Debashis; Chang, T. N.; Metzner, Thomas J.; Kang, Lei; Rijn, Matt van de; Skinner, Eila C.; Gambhir, Sanjiv S.; Weissman, Irving L.; Liao, Joseph C.

doi:10.1126/scitranslmed.3009457

Cited by 138 publications

(110 citation statements)

References 36 publications

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“…are sensitive to blocking anti-CD47 antibodies (233,234,(241)(242)(243)(244)(245)(246)(247)(248)(249)(250). This makes CD47 the first protooncogene that is universally expressed in all cancers; its function is known, and blockade of its function is therapeutic.…”

Section: Cancer Stem Cells and The Therapeutics That Come From Them: mentioning

confidence: 99%

How One Thing Led to Another

Weissman

2016

Annu. Rev. Immunol.

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I started research in high school, experimenting on immunological tolerance to transplantation antigens. This led to studies of the thymus as the site of maturation of T cells, which led to the discovery, isolation, and clinical transplantation of purified hematopoietic stem cells (HSCs). The induction of immune tolerance with HSCs has led to isolation of other tissue-specific stem cells for regenerative medicine. Our studies of circulating competing germline stem cells in colonial protochordates led us to document competing HSCs. In human acute myelogenous leukemia we showed that all preleukemic mutations occur in HSCs, and determined their order; the final mutations occur in a multipotent progenitor derived from the preleukemic HSC clone. With these, we discovered that CD47 is an upregulated gene in all human cancers and is a “don't eat me” signal; blocking it with antibodies leads to cancer cell phagocytosis. CD47 is the first known gene common to all cancers and is a target for cancer immunotherapy.

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Section: Cancer Stem Cells and The Therapeutics That Come From Them: mentioning

confidence: 99%

How One Thing Led to Another

Weissman

2016

Annu. Rev. Immunol.

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“…In patients lacking CD44v6 in BC tissue, there is a 2.3-fold increased risk of recurrence (95% confidence interval, 1.28-4.08) [41]. Pan et al [42] reported CD47 as a target for blue-light cystoscopy imaging of BC. The study found a sensitivity of 82.9% and a specificity of 90.5% for CD47-targeted imaging of BC.…”

Section: Discussionmentioning

confidence: 99%

Identification of Carbonic Anhydrase IX as a Novel Target for Endoscopic Molecular Imaging of Human Bladder Cancer

Wang

Fang

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Emerging novel optical imaging techniques with cancer-specific molecular imaging agents offer a powerful and promising platform for cancer detection and resection. White-light cystoscopy and random bladder biopsies remain the most appropriate but nonetheless suboptimal diagnostic technique for bladder cancer, which is associated with high morbidity and recurrence. However, white-light cystoscopy has intrinsic shortcomings. Although current optical imaging technologies hold great potential for improved diagnostic accuracy, there are few imaging agents for specific molecular targeting. Carbonic anhydrase IX (CAIX) plays a pivotal role in tumorigenesis and tumor progression with potential value as an imaging target. Here, we investigated the feasibility of CAIX as a target and validated the diagnostic performance and significance of CAIX as an imaging agent. Methods: We first analyzed the data from The Cancer Genome Atlas (TCGA). Pairs of samples comprising bladder cancer and adjacent normal tissue were collected. All tissue samples were used for real-time PCR and immunohistochemistry to compare CAIX expression in normal and cancer tissue. Using blue-light cystoscopy, we observed the optical distribution of fluorescently labeled CAIX antibody in freshly excised human bladders and obtained random bladder biopsies to assess sensitivity and specificity. Results: The TCGA data revealed that CAIX expression was significantly higher in bladder cancer specimens than in normal tissue. The outcome was similar in quantitative real-time PCR analysis. In immunohistochemical analysis, bladder cancer specimens classified in four pathological subtypes presented a variety of positive staining intensities, whereas no benign specimens showed CAIX staining. Using blue-light cystoscopy, we distinguished bladder cancers that were mainly papillary, some variants of urothelial carcinoma, and less carcinoma in situ, from benign tissue, despite the presence of suspicious-appearing mucosa. The sensitivity and specificity for CAIX-targeted imaging were 88.00% and 93.75%, respectively. Conclusions: CAIX-targeted molecular imaging could be a feasible and adaptive alternative approach for the accurate diagnosis and complete resection of bladder cancer.

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“…To achieve this goal, we will need tools to determine which properties of precancerous lesions predict the likelihood of progression to malignant metastatic disease. There are extraordinary opportunities in pushing these boundaries: (i) exploring new imaging technologies, sensors, and agents through engineering advances, (ii) combining blood biomarkers with imaging, and (iii) developing microscopic imaging tools that can be used intraoperatively or during minimally invasive procedures (i.e., microendoscopy) (49). Combining imaging and blood biomarker analysis may be particularly helpful in increasing the accuracy of screening procedures.…”

Section: Imaging Molecular and Cellular Biomarkersmentioning

confidence: 99%

“…Blood tests for circulating tumor DNA, microvesicles, circulating cancer cells, and/or other makers may increase the accuracy of CT screening (42,50,51). Intraoperative imaging with fluorescent affinity ligands or antibodies (52,53) is now a clinical reality, and reports from the first clinical trials are very promising (49,54). These approaches will ultimately change cancer surgery standards by giving surgeons realtime feedback about tumor margins and whether any cancer remains.…”

Section: Imaging Molecular and Cellular Biomarkersmentioning

confidence: 99%

Advancing biomedical imaging

Weissleder

Nahrendorf

2015

Proc. Natl. Acad. Sci. U.S.A.

158

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Imaging reveals complex structures and dynamic interactive processes, located deep inside the body, that are otherwise difficult to decipher. Numerous imaging modalities harness every last inch of the energy spectrum. Clinical modalities include magnetic resonance imaging (MRI), X-ray computed tomography (CT), ultrasound, and light-based methods [endoscopy and optical coherence tomography (OCT)]. Research modalities include various light microscopy techniques (confocal, multiphoton, total internal reflection, superresolution fluorescence microscopy), electron microscopy, mass spectrometry imaging, fluorescence tomography, bioluminescence, variations of OCT, and optoacoustic imaging, among a few others. Although clinical imaging and research microscopy are often isolated from one another, we argue that their combination and integration is not only informative but also essential to discovering new biology and interpreting clinical datasets in which signals invariably originate from hundreds to thousands of cells per voxel.

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Endoscopic molecular imaging of human bladder cancer using a CD47 antibody

Cited by 138 publications

References 36 publications

How One Thing Led to Another

How One Thing Led to Another

Identification of Carbonic Anhydrase IX as a Novel Target for Endoscopic Molecular Imaging of Human Bladder Cancer

Advancing biomedical imaging

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