An engineered anti-CA19-9 cys-diabody for positron emission tomography imaging of pancreatic cancer and targeting of polymerized liposomal nanoparticles

Girgis, Mark D.; Federman, Noah; Rochefort, Matthew M.; McCabe, Katelyn E.; Wu, Anna M.; Nagy, Jon O.; Denny, Christopher T.; Tomlinson, James S.

doi:10.1016/j.jss.2013.05.095

Cited by 26 publications

(16 citation statements)

References 33 publications

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“…Conventional monoclonal antibodies, monoclonal antibodies bound to radioactive isotopes and therapeutic nanoparticles, as well as, vaccines targeting CA19-9 are undergoing investigation (11, 15, 16). Thus, improved understanding and characterization of the role of CA 19-9 in MTC may make it amenable to novel therapies in the future.…”

Section: Discussionmentioning

confidence: 99%

Medullary Thyroid Cancer that Stains Negative for CA 19-9 has Decreased Metastatic Potential

et al. 2015

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Objective Presently, no clinical tools are available to diagnose the metastatic potential of medullary thyroid cancer (MTC) at disease presentation. Surveillance with calcitonin and carcinoembryonic antigen is currently recommended for observation and diagnosis of metastatic disease after initial treatment of MTC. Recently, CA 19-9 staining has been associated with aggressive forms of MTC and metastatic spread. This pilot study explores if positive CA19-9 staining of MTC tissue is associated with its metastatic potential. Methods Sixteen cases of MTC were identified and the specimens immunostained for CA 19-9 and other MTC tumor markers. Clinical information about patients’ MTC was collected through a retrospective chart review. Results 63% of the specimens stained positive for CA19-9. The median size of positively staining specimens was 2.6 cm (interquartile range 1.2 cm-3.2 cm) compared to 0.7cm (0.5 cm–1.2 cm) in negatively staining MTC specimens (p=0.04). All specimens from patients diagnosed with stage IV MTC, stained positive for CA19-9 compared to only 40% of cases that were classified as stage I-III (p=0.03). Furthermore, 100% of the primary specimens that were documented to have metastatic spread, stained positive for CA19-9. The sensitivity for ruling out stage IV MTC based on negative staining for CA 19-9 was 100%. Conclusion Based on these results we conclude that negative staining of MTC for CA19-9 may be associated with its decreased metastatic potential.

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Section: Discussionmentioning

confidence: 99%

Medullary Thyroid Cancer that Stains Negative for CA 19-9 has Decreased Metastatic Potential

et al. 2015

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“…Nevertheless, the location of the CA19-9 glycoprotein on the outermost layer of the cell membrane allows ease of antibody targeting, and Girgis and colleagues have demonstrated in a preclinical study the ability to target CA19-9 with radiolabelled anti CA19-9 antibodies to produce antigen-specific microPET images. This in turn promises to translate to therapeutic payloads targeted via engineered antibodies against CA19-9 and new systemic agents for bladder cancer [10].…”

Section: Discussionmentioning

confidence: 99%

Response of Serum Tumor Markers CA19-9 and bHCG to Cystectomy for Bladder Urothelial Carcinoma

Ho¹,

Hong²,

Norris³

et al. 2016

Ely J Can Res

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Tumor markers such as beta Human Chorionic Gonadotropin (bHCG) and Carboxyhydrate Antigen 19-9 (CA19-9) have long been associated with bladder cancer and although their expression is associated with poorer oncological outcomes, they have little role in the routine clinical management of this disease. Recent advances in engineered antibody technology have led to renewed interest in these markers as potential targets for new therapeutics. Here we report the case of a patient with locally advanced bladder cancer and the response of serum bHCG and CA19-9 to endoscopic resection and then radical cystectomy and serves to highlight how these tumor markers might be used to measure treatment effect.

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“…In addition to 5B1, a number anti-CA19.9 antibody fragments have recently been reported. [42–44] Antibody fragments are expected to increase tumor penetration and reduce the lag time between injection and imaging, providing a benefit to patients in terms of time spent in the clinic and exposure to radiation. While initial results with many of the anti-CA19.9 tracers are promising, murine models lack any endogenous expression of CA19.9 and until more biologically relevant murine models are developed or clinical data in humans becomes available, the utility of these tracers will remain uncertain.…”

Section: Circulating Tumor Biomarkersmentioning

confidence: 99%

Challenges of Pancreatic Cancer

Dimastromatteo¹,

Houghton²,

Lewis³

et al. 2015

The Cancer Journal

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The development of novel molecular cancer imaging agents has considerably advanced in recent years. Numerous cancer imaging agents have demonstrated remarkable potential for aiding the diagnosis, staging, and treatment planning at the preclinical stage which in turn has led to a number of agents being approved for human trials. Pancreatic ductal adenocarcinoma (PDAC) is currently the most deadly common carcinoma with an overall 5-year survival rate of about 6%. As detection technologies progress, the need for molecular imaging tools that will allow the diagnosis at an early stage will be crucial to improving patient outcomes. In this review, we will highlight agents that illuminate various cell populations that comprise the tumor: epithelial, endothelial, and stromal tumor cells.

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An engineered anti-CA19-9 cys-diabody for positron emission tomography imaging of pancreatic cancer and targeting of polymerized liposomal nanoparticles

Abstract: Published by Elsevier Inc.

Cited by 26 publications

References 33 publications

Medullary Thyroid Cancer that Stains Negative for CA 19-9 has Decreased Metastatic Potential

Medullary Thyroid Cancer that Stains Negative for CA 19-9 has Decreased Metastatic Potential

Response of Serum Tumor Markers CA19-9 and bHCG to Cystectomy for Bladder Urothelial Carcinoma

Challenges of Pancreatic Cancer

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