Develop companion radiopharmaceutical YKL40 antibodies as potential theranostic agents for epithelial ovarian cancer

Chang, Ming; Chiang, Ping-Fang; Kuo, Yu-Jen; Peng, Cheng‐Liang; Chen, I.-Chun; Huang, Chia-Yen; Chen, Chi-An; Chiang, Yi-Te

doi:10.1016/j.biopha.2022.113668

Cited by 5 publications

(4 citation statements)

References 38 publications

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“…CHI3L1 (YKL40) may play an important role in the complex processes involved in cancer progression; therefore, while modulating CHI3L1 (YKL40) may not be sufficient to comprehensively treat all cancers, it shows promise against some cancers. Based on a neutralizing mAb, our group demonstrated the use of a radioisotope-conjugated antibody to generate a novel radiopharmaceutical for inhibiting ovarian cancer progression [ 72 ]. Our study demonstrated that the radiopharmaceutical significantly inhibited tumor growth in ovarian cancer xenograft mice, which is a promising result [ 72 ].…”

Section: Chi3l1 (Ykl40)—related Therapymentioning

confidence: 99%

“…Based on a neutralizing mAb, our group demonstrated the use of a radioisotope-conjugated antibody to generate a novel radiopharmaceutical for inhibiting ovarian cancer progression [ 72 ]. Our study demonstrated that the radiopharmaceutical significantly inhibited tumor growth in ovarian cancer xenograft mice, which is a promising result [ 72 ].…”

Section: Chi3l1 (Ykl40)—related Therapymentioning

confidence: 99%

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The Role of Chitinase-3-like Protein-1 (YKL40) in the Therapy of Cancer and Other Chronic-Inflammation-Related Diseases

Chang,

Chen,

Chiang

et al. 2024

Pharmaceuticals

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Chitinase-3-like protein-1 (CHI3L1), also known as YKL40, is a glycoprotein that belongs to the chitinase protein family. It is involved in various biological functions, including cell proliferation and tissue remodeling, with inflammatory and immunomodulatory capabilities. Several studies have shown that CHI3L1(YKL40) is upregulated in various diseases, such as cancer, asthma, and inflammatory bowel disease, among others. Although the expression level of CHI3L1(YKL40) is associated with disease activity, severity, and prognosis, its potential as a therapeutic target is still under investigation. In this review, we summarize the biological functions, pathological roles, and potential clinical applications of specific inhibitors and targeted therapies related to CHI3L1(YKL40).

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Section: Chi3l1 (Ykl40)—related Therapymentioning

confidence: 99%

Section: Chi3l1 (Ykl40)—related Therapymentioning

confidence: 99%

The Role of Chitinase-3-like Protein-1 (YKL40) in the Therapy of Cancer and Other Chronic-Inflammation-Related Diseases

Chang,

Chen,

Chiang

et al. 2024

Pharmaceuticals

Self Cite

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“…CHI3L1 is implicated in promoting ovarian cancer cell proliferation, invasion, migration, tumor angiogenesis, chemoresistance, and has significant potential as a theranostic target (Shao et al, 2009). While CHI3L1 antibodies have high affinity for EOC cells, they do not directly induce apoptosis in vivo as a stand-alone (Chang et al, 2022). However, conjugating the antibodies with a therapeutic radionuclide Lu-177 complex has been shown to enhance its stability and anti-tumor efficacy in a mouse xenograft model.…”

Section: Potential Of Miscellaneous Biomarker Candidates To Advance F...mentioning

confidence: 99%

Future theranostic strategies: emerging ovarian cancer biomarkers to bridge the gap between diagnosis and treatment

Rajapaksha,

Khetan,

Johnson

et al. 2024

Front. Drug Deliv.

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Ovarian cancers are a complex and heterogenic group of malignancies that are difficult to detect, diagnose and treat. Fortunately, considerable knowledge of ovarian cancer specific biomarkers has been generated, that is pertinent to the development of novel theranostic platforms by combining therapies and diagnostics. Genomic and proteomic data has been invaluable in providing critical biomolecular targets for ovarian cancer theranostic approaches. Exploitation of the wealth of biomarker research that has been conducted offers viable targets as beacons for ovarian cancer detection, diagnosis, and therapeutic targeting. These markers can be used in theranostics, a treatment strategy that combines therapy and diagnostics and is common in nuclear medicine, where radionuclides are used for both diagnosis and treatment. The development of theranostics has taken substantial focus in recent years in the battle against ovarian cancer. Yet to date only one theranostic technology has emerged in clinical practice. However, given the wealth of ovarian cancer biomarkers the field is poised to see the emergence of revolutionary disease treatment and monitoring outcomes through their incorporation into the development of theranostic strategies. The future of ovarian cancer treatment is set to enable precise diagnosis, targeted treatment, and vigilant monitoring. This review aims to assess the status of ovarian cancer diagnostic tools and biomarkers in practice, clinical development, or pre-clinical development, highlighting newly emerging theranostic applications.

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“…The combination of antibody labeling and bio-imaging techniques plays an important role in establishing the in vivo distribution characteristics of novel antibody molecules. This approach has been increasingly adopted because of its ability to provide a comprehensive understanding of tumor biology as well as its specific binding affinity toward the intended targets [ 14 , 15 , 16 ]. Therefore, we applied autoradiography and single photon emission computer tomography (SPECT) imaging technology to obtain direct visual verification of the distribution properties of 125 I-LR004.…”

Section: Introductionmentioning

confidence: 99%

Preclinical Pharmacokinetics and Biodistribution of LR004, a Novel Antiepidermal Growth Factor Receptor Monoclonal Antibody

Zheng,

Dou,

Liu

et al. 2024

Molecules

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LR004 is a novel chimeric (human/mouse) monoclonal antibody developed for the treatment of advanced colorectal carcinoma with detectable epidermal growth factor receptor (EGFR) expression. We aimed to investigate the preclinical pharmacokinetics (PK) and in vivo biodistribution of LR004. The PK profiles of LR004 were initially established in rhesus monkeys. Subsequently, 125I radionuclide-labeled LR004 was developed and the biodistribution, autoradiography, and NanoSPECT/CT of 125I-LR004 in xenograft mice bearing A431 tumors were examined. The PK data revealed a prolonged half-life and nonlinear PK characteristics of LR004 within the dose range of 6–54 mg/kg. The radiochemical purity of 125I-LR004 was approximately 98.54%, and iodination of LR004 did not affect its specific binding activity to the EGFR antigen. In a classical biodistribution study, 125I-LR004 exhibited higher uptake in highly perfused organs than in poorly perfused organs. Prolonged retention properties of 125I-LR004 in tumors were observed at 4 and 10 days. Autoradiography and NanoSPECT/CT confirmed the sustained retention of 125I-LR004 at the tumor site in xenograft mice. These findings demonstrated the adequate tumor targeting capabilities of 125I-LR004 in EGFR-positive tumors, which may improve dosing strategies and future drug development.

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Develop companion radiopharmaceutical YKL40 antibodies as potential theranostic agents for epithelial ovarian cancer

Cited by 5 publications

References 38 publications

The Role of Chitinase-3-like Protein-1 (YKL40) in the Therapy of Cancer and Other Chronic-Inflammation-Related Diseases

The Role of Chitinase-3-like Protein-1 (YKL40) in the Therapy of Cancer and Other Chronic-Inflammation-Related Diseases

Future theranostic strategies: emerging ovarian cancer biomarkers to bridge the gap between diagnosis and treatment

Preclinical Pharmacokinetics and Biodistribution of LR004, a Novel Antiepidermal Growth Factor Receptor Monoclonal Antibody

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