Establishment of a novel anti-TROP2 monoclonal antibody TrMab-29 for immunohistochemical analysis

Sayama, Yusuke; Kaneko, Mika K.; Takei, Junko; Hosono, Hideki; Sano, M.; Asano, Teizo; Kato, Yukinari

doi:10.1016/j.bbrep.2020.100902

Cited by 28 publications

(15 citation statements)

References 38 publications

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“…The CBIS method can help us effectively develop mAbs that are useful in flow cytometry. We recently succeeded in developing numerous useful mAbs that target membrane proteins, including podoplanin ( 58 – 61 ), CD20 ( 62 ), CD44 ( 63 ), CD133 ( 54 ), and TROP2 ( 64 , 65 ). Importantly, these mAbs are very useful for various experiments, including not only flow cytometry, but also western blot analysis and immunohistochemistry.…”

Section: Discussionmentioning

confidence: 99%

Anti‑HER3 monoclonal antibody exerts antitumor activity in a mouse model of colorectal adenocarcinoma

et al. 2021

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HER3 belongs to the epidermal growth factor receptor (EGFR) family and is known to form an active heterodimer with other three family members EGFR, HER2, and HER4. HER3 is overexpressed in lung, breast, colon, prostate, and gastric cancers. In the present study, we developed and validated an anti-HER3 monoclonal antibody (mAb), H 3 Mab-17 (IgG 2a , kappa), by immunizing mice with HER3-overexpressed CHO-K1 cells (CHO/HER3). H 3 Mab-17 was found to react specifically with endogenous HER3 in colorectal carcinoma cell lines, using flow cytometry. The K D for H 3 Mab-17 in CHO/HER3 and Caco-2 (a colon cancer cell line) were determined to be 3.0x10 -9 M and 1.5x10 -9 M via flow cytometry, respectively, suggesting high binding affinity of H 3 Mab-17 to HER3. Then, we assessed the H 3 Mab-17 antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against Caco-2, and evaluated its antitumor capacity in a Caco-2 xenograft model. In vitro experiments revealed H 3 Mab-17 had strongly induced both ADCC and CDC against Caco-2 cells. In vivo experiments on Caco-2 xenografts revealed that H 3 Mab-17 treatment significantly reduced tumor growth compared with the control mouse IgG. These data indicated that H 3 Mab-17 could be a promising treatment option for HER3-expressing colon cancers.

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Section: Discussionmentioning

confidence: 99%

Anti‑HER3 monoclonal antibody exerts antitumor activity in a mouse model of colorectal adenocarcinoma

et al. 2021

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“…Although these data are not practice‐changing, because sacituzumab govitecan outperformed chemotherapy in all expression subgroups, the future availability of additional treatment options in this setting may render biomarker selection more relevant for clinical decision making. Also, better assays for Trop‐2 assessment may further refine our ability to select patients, allowing us to optimally analyze Trop‐2 expression in BC and other cancer histologies 100,101 . Similarly, nectin‐4 expression was also recently shown to relevantly influence the activity of enfortumab vedotin in preclinical experiments, 102 warranting the confirmation of this observation in the clinic.…”

Section: The Conundrum Of Predictive Biomarkers For Adc Activitymentioning

confidence: 94%

Antibody–drug conjugates: Smart chemotherapy delivery across tumor histologies

Tarantino

Pestana

Corti

et al. 2021

CA A Cancer J Clinicians

222

115

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As distinct cancer biomarkers have been discovered in recent years, a need to reclassify tumors by more than their histology has been proposed, and therapies are now tailored to treat cancers based on specific molecular aberrations and immunologic markers. In fact, multiple histology‐agnostic therapies are currently adopted in clinical practice for treating patients regardless of their tumor site of origin. In parallel with this new model for drug development, in the past few years, several novel antibody–drug conjugates (ADCs) have been approved to treat solid tumors, benefiting from engineering improvements in the conjugation process and the introduction of novel linkers and payloads. With the recognition that numerous surface targets are expressed across various cancer histologies, alongside the remarkable activity of modern ADCs, this drug class has been increasingly evaluated as suitable for a histology‐agnostic expansion of indication. For illustration, the anti‐HER2 ADC trastuzumab deruxtecan has demonstrated compelling activity in HER2‐overexpressing breast, gastric, colorectal, and lung cancer. Examples of additional novel and potentially histology‐agnostic ADC targets include trophoblast cell‐surface antigen 2 (Trop‐2) and nectin‐4, among others. In the current review article, the authors summarize the current approvals of ADCs by the US Food and Drug Administration focusing on solid tumors and discuss the challenges and opportunities posed by the multihistological expansion of ADCs.

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“…Therefore, the establishment of anti-EpCAM mAbs is important to improve the efficacy of the abovementioned applications and to develop novel modalities for tumor therapy. In this study, we developed anti-EpCAM mAbs using the Cell-Based Immunization and Screening (CBIS) method [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ], and evaluated it for various applications, including flow cytometry, Western blotting, and immunohistochemical analyses.…”

Section: Introductionmentioning

confidence: 99%

Development of a Novel Anti-EpCAM Monoclonal Antibody for Various Applications

Suzuki

Asano

et al. 2022

Antibodies

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The epithelial cell adhesion molecule (EpCAM) is a cell surface glycoprotein, which is widely expressed on normal and cancer cells. EpCAM is involved in cell adhesion, proliferation, survival, stemness, and tumorigenesis. Therefore, EpCAM is thought to be a promising target for cancer diagnosis and therapy. In this study, we established anti-EpCAM monoclonal antibodies (mAbs) using the Cell-Based Immunization and Screening (CBIS) method. We characterized them using flow cytometry, Western blotting, and immunohistochemistry. One of the established recombinant anti-EpCAM mAbs, recEpMab-37 (mouse IgG1, kappa), reacted with EpCAM-overexpressed Chinese hamster ovary-K1 cells (CHO/EpCAM) or a colorectal carcinoma cell line (Caco-2). In contrast, recEpMab-37 did not react with EpCAM-knocked out Caco-2 cells. The KD of recEpMab-37 for CHO/EpCAM and Caco-2 was 2.0 × 10−8 M and 3.2 × 10−8 M, respectively. We observed that EpCAM amino acids between 144 to 164 are involved in recEpMab-37 binding. In Western blot analysis, recEpMab-37 detected the EpCAM of CHO/EpCAM and Caco-2 cells. Furthermore, recEpMab-37 could stain formalin-fixed paraffin-embedded colorectal carcinoma tissues by immunohistochemistry. Taken together, recEpMab-37, established by the CBIS method, is useful for detecting EpCAM in various applications.

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Establishment of a novel anti-TROP2 monoclonal antibody TrMab-29 for immunohistochemical analysis

Cited by 28 publications

References 38 publications

Anti‑HER3 monoclonal antibody exerts antitumor activity in a mouse model of colorectal adenocarcinoma

Anti‑HER3 monoclonal antibody exerts antitumor activity in a mouse model of colorectal adenocarcinoma

Antibody–drug conjugates: Smart chemotherapy delivery across tumor histologies

Development of a Novel Anti-EpCAM Monoclonal Antibody for Various Applications

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