作者: Mojica, Wilfrido ; Su, Yafei ; Rittenhouse-Olson, Kate ; Attwood, Kristopher M ; Attwood, Kristopher M. ; Hsu, Chang-Chieh ; Wu, Yun ; Dy, Grace K ; Reid, Mary E ; Dy, Grace K. ; Reid, Mary E.

Abstract:

Exosomes are nanosized extracellular vesicles released by cells to transport biomolecules such as proteins and RNAs for intercellular communication. Exosomes play important roles in cancer development and metastasis; therefore, they have emerged as potential liquid biopsy biomarkers for cancer screening, diagnosis, and management. Many exosome cargos, including proteins, RNAs, and lipids, have been extensively investigated as biomarkers for cancer liquid biopsy. However, carbohydrates, an important type of biomolecule, have not yet been explored for this purpose. In this study, we reported a new exosomal carbohydrate biomarker, α-linked Thomsen–Friedenreich glycoantigen (TF-Ag-α; Galβ1-3GalNAc-α). To translate our discovery into clinical settings, we developed a surface plasmon resonance–based assay which utilized a unique mAb, JAA-F11, with high specificity to measure the levels of exosomal TF-Ag-α in blood. To the best of our knowledge, we are the first to demonstrate that exosomes carry TF-Ag-α. We detected exosomal TF-Ag-α in as low as 10 μL serum samples from patients with cancer, but in contrast, levels were negligible in those from normal controls. With a total of 233 patients with cancer and normal controls, we showed that exosomal TF-Ag-α detected lung cancer (n = 60) and breast cancer (n = 95) from normal controls (n = 78) with ≥95% and ≥97% accuracy, respectively. These results demonstrated that exosomal TF-Ag-α is a potential liquid biopsy biomarker for cancer diagnosis.

Significance::

Exosomes or small extracellular vesicles have emerged as potent biomarkers of cancer liquid biopsy. We discovered a new exosomal carbohydrate marker, TF-Ag-α (Galβ1-3GalNAc-α), and showed that exosomal TF-Ag-α detected both lung and breast cancers with >95% accuracy. Our findings demonstrated that exosomal TF-Ag-α is a promising liquid biopsy biomarker for cancer screening and early detection.

2018-04-01·Translational oncology3区 · 医学

Preclinical Analysis of JAA-F11, a Specific Anti–Thomsen-Friedenreich Antibody via Immunohistochemistry and In Vivo Imaging

3区 · 医学

ArticleOA

作者: Ludwig, Rachel ; Tati, Swetha ; Adams, Julia ; Roy, Rene ; Rittenhouse-Olson, Kate ; Johnson, Holly ; Ghazal, Diala ; Karacosta, Loukia G ; Koury, Steven ; Sajjad, Munawwar ; Olson, James R ; Turner, Bradley ; Jessee, Joseph ; Fisk, John C

The tumor specificity of JAA-F11, a novel monoclonal antibody specific for the Thomsen-Friedenreich cancer antigen (TF-Ag-alpha linked), has been comprehensively studied by in vitro immunohistochemical (IHC) staining of human tumor and normal tissue microarrays and in vivo biodistribution and imaging by micro-positron emission tomography imaging in breast and lung tumor models in mice. The IHC analysis detailed herein is the comprehensive biological analysis of the tumor specificity of JAA-F11 antibody performed as JAA-F11 is progressing towards preclinical safety testing and clinical trials. Wide tumor reactivity of JAA-F11, relative to the matched mouse IgG₃ (control), was observed in 85% of 1269 cases of breast, lung, prostate, colon, bladder, and ovarian cancer. Staining on tissues from breast cancer cases was similar regardless of hormonal or Her2 status, and this is particularly important in finding a target on the currently untargetable triple-negative breast cancer subtype. Humanization of JAA-F11 was recently carried out as explained in a companion paper "Humanization of JAA-F11, a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody and In Vitro Efficacy Analysis" (Neoplasia 19: 716-733, 2017), and it was confirmed that humanization did not affect chemical specificity. IHC studies with humanized JAA-F11 showed similar binding to human breast tumor tissues. In vivo imaging and biodistribution studies in a mouse syngeneic breast cancer model and in a mouse-human xenograft lung cancer model with humanized ¹²⁴I- JAA-F11 construct confirmed in vitro tumor reactivity and specificity. In conclusion, the tumor reactivity of JAA-F11 supports the continued development of JAA-F11 as a targeted cancer therapeutic for multiple cancers, including those with unmet need.

2018-01-01·Neoplasia (New York, N.Y.)2区 · 医学

Corrigendum to “Humanization of JAA-F11, a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody and In Vitro Efficacy Analysis” [Neoplasia 19.9 (2017) 716-733]

2区 · 医学

ArticleOA

作者: Chrisikos, Taylor ; Rittenhouse-Olson, Kate ; Koury, Stephen ; Quataert, Sally ; Abdullah, Julia ; Zalzala, Fatma ; Philbin, Padraic ; Morey, Susan ; Eng, Jing Ying ; Glinsky, Vladislav V ; Glinskii, Olga V ; Ghazal, Diala ; Moreno, David ; Karacosta, Loukia ; Sesay, Muctarr ; Olson, James R ; Tati, Swetha ; Gebhard, Anthony W ; Birthare, Karamverr ; Jessee, Joseph ; Fisk, John C

100 项与 JAA-F11 相关的药物交易

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