A novel target anti-interleukin-13 receptor subunit alpha-2 monoclonal antibody inhibits tumor growth and metastasis in lung cancer

Raza, Ghulam Shere; Yunus, Fakhar-un-Nisa; Mangukiya, Hitesh Bhagavanbhai; Merugu, Siva Bharath; Mashausi, Dhahiri Saidi; Zeling, Wang; Negi, Hema; Zhou, Bingjie; Roy, Debmalya; Wu, Zhenghua; Li, Dawei

doi:10.1016/j.intimp.2020.107155

Cited by 5 publications

(3 citation statements)

References 39 publications

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“…In IL-13Rα2-positive pancreatic cancer, the possibility of celiac plexus invasion can be predicted in advance of surgery, and it may be possible to manage the pain in the patients receiving chemotherapy. Raza et al developed an anti-IL-13Rα2-based novel therapy for assessing its antitumor effect in a mouse model of lung cancer [ 34 ]. The anti-IL-13Rα2 antibody reduced tumor metastasis and prolonged the prognosis in this model.…”

Section: Future Diagnostic and Prognostic Trends For Pancreatic Cancer In The Context Of Il-13rα2 Expressionmentioning

confidence: 99%

IL-13Rα2 Is a Biomarker of Diagnosis and Therapeutic Response in Human Pancreatic Cancer

et al. 2021

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IL-13Rα2 is a high-affinity binding protein for its ligand IL-13 and a cancer-testis antigen as it is expressed in the testis. IL-13Rα2 is highly expressed in various cancers, including pancreatic cancer, and consists of three domains: extracellular, transmembrane, and cytoplasmic. The extracellular domain binds to the ligand to form a biologically active complex, which initiates signaling through AP-1 and other pathways. IL-13Rα2 is also expressed in diseased cells such as fibroblasts that are involved in various inflammatory diseases, including cancer. We have reported that IL-13Rα2 is a prognostic biomarker for malignant glioma, adrenocortical cancer, and pancreatic cancer. In pancreatic cancer, a small sample of tissue could be examined for the expression of IL-13Rα2 by using the endoscopic ultrasound-fine needle aspiration technique (EUS-FNA). In addition, a peptide-based targeted approach using Pep-1L peptide could be used to study the biodistribution and whole-body cancer imaging for the screening of pancreatic cancer in suspected subjects.

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Section: Future Diagnostic and Prognostic Trends For Pancreatic Cancer In The Context Of Il-13rα2 Expressionmentioning

confidence: 99%

IL-13Rα2 Is a Biomarker of Diagnosis and Therapeutic Response in Human Pancreatic Cancer

et al. 2021

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“…One of the receptors targeted in several cancers is IL13Rα2, a variant of the IL-13 receptor. Although the overexpression of IL13Rα2 has been primarily reported in glioblastoma, breast, ovarian, colorectal and pancreatic cancer, more studies are needed for a better understanding of the clinical importance of IL13Rα2 targeting in a variety of cancers (13)(14)(15). As shown in another study, more than 50% of glioblastoma (GBM) cells express IL13Rα2.…”

mentioning

confidence: 95%

“…Accordingly, we showed a reasonable fact of using the IL13-PE toxin fusion in targeted therapy strategies against different cancers bearing the cognate receptor, IL13Rα2. To our knowledge, although it has been previously shown that IL13Rα2 can be targeted in lung cancer, and one study suggest IL13Rα2 specific monoclonal antibody therapy, no detailed study of IL13Rα2 targeted recombinant toxins have been reported against lung cancer (15,24). The anti-cancer effects of IL13-PE were then analyzed in lung cancer cell lines.…”

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confidence: 99%

IL13 Fused Pseudomonas Exotoxin Targets Various Cancers In Vitro

Uludağ

Karakaş

2021

Anticancer Res

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Background/Aim: Pseudomonas exotoxin (PE) is one of the most widely used toxins in the construction of therapeutic fusion proteins in pre-clinical studies followed by phase trials. In principle, PE acts by blocking protein synthesis through catalyzing the inactivation of elongation factor-2 (EF-2). The interleukin-13 fused PE (IL13-PE) cytotoxin was previously designed to target GBM cells. In this study, the cytotoxic effects of IL13-PE were evaluated in 5 different types of cancers and the therapeutic effects were further analyzed in a lung cancer cell line, NCI-H460. Conceptually, in another lung cancer cell line (A549), IL13Rα2 was overexpressed by lentiviruses (A549-IL13Rα2) and evaluated for cytotoxic efficacy of IL13-PE. Materials and Methods: The expression profile of IL13Rα2 in different cancer cell lines was determined by RT-PCR. Secretable toxin fusion was expressed in the toxin resistant HEK-293T cell line (293T-TxR) by using a plasmid coding for IL13-PE and IRES-GFP (LV-IL13-PE-IRES/GFP). Next, the cells were shown to produce and secrete functional IL13-PE by dot blot analysis, followed by cell viability assays and cell death analysis. Results: Upon treatment with IL13-PE, a significant decrease in cell viability was selectively demonstrated in cancer cells with cognate receptor expression. IL13-PE treatment increased the apoptotic/necrotic cell populations in the NCI-H460 cell line. Conclusion:Our results demonstrate that IL13-PE can be a therapeutic target for tumors bearing mostly IL13Rα2 positive cell populations. Our findings also suggest a cell-based delivery option for the recombinant toxins in the treatment of different cancers which can provide a solution for the clinical use of toxin therapy.

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Interleukin 13 receptor alpha 2 (IL13Rα2): Expression, signaling pathways and therapeutic applications in cancer

Jaén

Martín‐Regalado²,

Bartolomé³

et al. 2022

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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A novel target anti-interleukin-13 receptor subunit alpha-2 monoclonal antibody inhibits tumor growth and metastasis in lung cancer

Cited by 5 publications

References 39 publications

IL-13Rα2 Is a Biomarker of Diagnosis and Therapeutic Response in Human Pancreatic Cancer

IL-13Rα2 Is a Biomarker of Diagnosis and Therapeutic Response in Human Pancreatic Cancer

IL13 Fused Pseudomonas Exotoxin Targets Various Cancers In Vitro

Interleukin 13 receptor alpha 2 (IL13Rα2): Expression, signaling pathways and therapeutic applications in cancer

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