Circulating tumor cells in precision medicine: challenges and opportunities

Rupp, Brittany; Ball, Harrison; Wuchu, Fulei; Nagrath, Deepak; Nagrath, Sunitha

doi:10.1016/j.tips.2022.02.005

Cited by 69 publications

(50 citation statements)

References 114 publications

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“…Clinically, circulating-tumor cells (CTCs), which express EpCAM, MET, and CD44, identifies a subset with increased metastasis-initiating phenotype [35], suggesting that CD44v6 plays an important role in cancer-initiating cell property cooperating with MET. In addition, CTC culture methods, including two-dimensional (2D) expansion, 3D organoids/spheroids culture, and xenograft formation in mice, have been developed to evaluate the character of CTCs [36]. Therefore, the biological property to affect cell proliferation and invasiveness by C44Mab-9 should be investigated because CD44v6 can potentiate the MET signaling by forming the ternary complex with HGF [37].…”

Section: Discussionmentioning

confidence: 99%

Development of a Novel Anti-CD44 variant 6 Monoclonal Antibody for Multiple Applications against Colorectal Carcinomas

Ejima¹,

Suzuki²,

Tanaka³

et al. 2023

Preprint

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CD44 is a cell surface glycoprotein, and its isoforms are produced by the alternative splicing with the standard and variant exons. The CD44 variant exon containing isoforms (CD44v) are overexpressed in carcinomas. CD44v6 is one of the CD44v, and its overexpression predicts poor prognosis in colorectal cancer (CRC) patients. CD44v6 plays critical roles in CRC adhesion, proliferation, stemness, invasiveness, and chemoresistance. Therefore, CD44v6 is a promising target for cancer diagnosis and therapy for CRC. In this study, we established anti-CD44 monoclonal antibodies (mAbs) by immunizing mice with CD44v3-10-overexpressed Chinese hamster ovary-K1 (CHO) cells. We then characterized them using enzyme-linked immunosorbent assay, flow cytometry, western blotting, and immunohistochemistry. One of the established clones (C44Mab-9; IgG1, kappa) reacted with a peptide of variant 6-encoded region, indicating that C44Mab-9 recognizes CD44v6. Furthermore, C44Mab-9 reacted with CHO/CD44v3-10 cells or CRC cell lines (COLO201 and COLO205) by flow cytometry. The apparent KD of C44Mab-9 for CHO/CD44v3-10, COLO201, and COLO205 was 8.1 × 10−9 M, 1.7 × 10−8 M, and 2.3 × 10−8 M, respectively. C44Mab-9 detected the CD44v3-10 in western blotting, and partially stained the formalin-fixed paraffin-embedded CRC tissues in immunohistochemistry. Collectively, C44Mab-9 is useful for detecting CD44v6 in various applications.

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Section: Discussionmentioning

confidence: 99%

Development of a Novel Anti-CD44 variant 6 Monoclonal Antibody for Multiple Applications against Colorectal Carcinomas

Ejima¹,

Suzuki²,

Tanaka³

et al. 2023

Preprint

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show abstract

“…Recently, CTC expansion techniques have been developed to evaluate the characteristics of CTCs. The techniques include the two-dimensional (2D) long-term expansion, 3D organoids/spheroids culture, and in vivo xenografts/metastasis formation in immunodeficient mice [ 58 ]. It would be worthwhile to investigate the effect of EpMab-37-mG 2a -f on the 2D and 3D CTC expansion in vitro and anti-metastatic activity in vivo.…”

Section: Discussionmentioning

confidence: 99%

A Defucosylated Anti-EpCAM Monoclonal Antibody (EpMab-37-mG2a-f) Exerts Antitumor Activity in Xenograft Model

et al. 2022

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The epithelial cell adhesion molecule (EpCAM) is a stem cell and carcinoma antigen, which mediates cellular adhesion and proliferative signaling by the proteolytic cleavage. In contrast to low expression in normal epithelium, EpCAM is frequently overexpressed in various carcinomas, which correlates with poor prognosis. Therefore, EpCAM has been considered as a promising target for tumor diagnosis and therapy. Using the Cell-Based Immunization and Screening (CBIS) method, we previously established an anti-EpCAM monoclonal antibody (EpMab-37; mouse IgG1, kappa). In this study, we investigated the antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and an antitumor activity by a defucosylated mouse IgG2a-type of EpMab-37 (EpMab-37-mG2a-f) against a breast cancer cell line (BT-474) and a pancreatic cancer cell line (Capan-2), both of which express EpCAM. EpMab-37-mG2a-f recognized BT-474 and Capan-2 cells with a moderate binding-affinity [apparent dissociation constant (KD): 2.9 × 10−8 M and 1.8 × 10−8 M, respectively] by flow cytometry. EpMab-37-mG2a-f exhibited ADCC and CDC for both cells by murine splenocytes and complements, respectively. Furthermore, administration of EpMab-37-mG2a-f significantly suppressed the xenograft tumor development compared with the control mouse IgG. These results indicated that EpMab-37-mG2a-f exerts antitumor activities and could provide valuable therapeutic regimen for breast and pancreatic cancers.

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“…CTC as a modality of liquid biopsy has been widely studied in a variety of cancer types. Low yield and the lack of appropriate downstream analyses for clinical use have limited application and development [ 23 ]. In this study, we validated the feasibility of increasing sampling volume by doing DLA, and processing the whole leukopak by using the AdnaTest procedure.…”

Section: Discussionmentioning

confidence: 99%

RNA profiling of circulating tumor cells systemically captured from diagnostic leukapheresis products in prostate cancer patients

Dong¹,

Du²,

Lu³

et al. 2022

Materials Today Bio

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Circulating tumor cells in precision medicine: challenges and opportunities

Cited by 69 publications

References 114 publications

Development of a Novel Anti-CD44 variant 6 Monoclonal Antibody for Multiple Applications against Colorectal Carcinomas

Development of a Novel Anti-CD44 variant 6 Monoclonal Antibody for Multiple Applications against Colorectal Carcinomas

A Defucosylated Anti-EpCAM Monoclonal Antibody (EpMab-37-mG2a-f) Exerts Antitumor Activity in Xenograft Model

RNA profiling of circulating tumor cells systemically captured from diagnostic leukapheresis products in prostate cancer patients

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