A dual-specific IGF-I/II human engineered antibody domain inhibits IGF signaling in breast cancer cells

Chen, Zhizhen; Liu, Jie; Chu, Dafeng; Shan, Yaming; Ma, Guixing; Zhang, Hongmin; Zhang, Xiaohua Douglas; Wang, Pu; Chen, Qiang; Deng, Chu‐Xia; Chen, Weizao; Dimitrov, Dimiter S.; Zhao, Qi

doi:10.7150/ijbs.25928

Cited by 10 publications

(8 citation statements)

References 41 publications

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“…There were no FDA drugs for IGFBP6, FOSB, and WLS. Further analysis showed that these three proteins interact with the well-known BRCA related proteins IGF1 [14][15][16] [14][15][16], FOS [17][18][19] [17][18][19],and WNT1 [20][21][22] [20][21][22], suggested that IGFBP6, FPSB, and FOS might be useful target for BRCA treatment. Survival analysis of the 7 DEGs…”

Section: Discussionmentioning

confidence: 99%

Integrated bioinformatics analysis identifies core genes in breast cancer

Niu¹,

Zhang²,

Yu³

et al. 2019

Preprint

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Background Breast cancer (BRCA) is one of the most common malignancies in women. To reveal the molecular mechanism of the BRCA, the core genes associated with BRCA was studied by the integrated bioinformatics methods in the current study. Results A total of 1181 DEGs, 84 DEGs, and 190 DEGs were detected in GSE7904, GSE10797, and GSE103512, respectively. In addition, 7 hub genes overlapped from 3 datasets were selected, and ANNXA1, MYH11, IGFBP6, FOS, FOSB, KIT, and WLS might be the core genes of BRCA. The Go function analysis showed that the DEGs were enriched in chromosome segregation, gland development, leukocyte migration, extracellular structure organization and so on. The KEGG pathway analysis showed that the most DEGs were enriched in Pathways in cancer, Focal adhesion, ECM-receptor interaction, PPAR signaling pathway, etc. Additionally, ANXA1 was associated with worse overall survival, and the other 6 hub genes were associated with better overall survival. Conclusions ANNXA1, MYH11, IGFBP6, FOS, FOSB, KIT, and WLS might be the core genes of BRCA. WLS, IGFBP6, and FOSB might be a new biomarker of the breast tumor and potential new drug targets. This study provided new evidence for the future genomic individualized treatment of BRCA.

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Section: Discussionmentioning

confidence: 99%

Integrated bioinformatics analysis identifies core genes in breast cancer

Niu¹,

Zhang²,

Yu³

et al. 2019

Preprint

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“…Anti-IGF-1R mAbs do not inhibit the hybrid receptor IGF-1R/IR-A mediated signaling. Inhibition of IGF-1R signaling can also be bypassed by IGF-II dependent IR-A activation [15,16]. Several types of antibodies, including mAbs, bispecific antibodies, and antibody fragments, against IGF-II have been reported [15][16][17][18], which markedly deactivate the IGF-1R/IR and affect tumor growth.…”

Section: Ivyspring International Publishermentioning

confidence: 99%

An insulin growth factor-I/II-neutralizing monoclonal antibody in combination with epidermal growth factor receptor inhibitors potently inhibits tumor cell growth

Ma¹,

Tan²,

Shan³

et al. 2022

J. Cancer

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The insulin-like growth factors (IGFs), IGF-1 and IGF-II, which bind to the IGF receptor type 1 (IGF-1R) and the insulin receptor (IR), have been implicated in the growth, survival, and metastasis of tumor cells. We have previously identified a novel human monoclonal antibody (mAb), m708.5, which neutralizes both human IGF-I and IGF-II, and potently inhibits phosphorylation of the IGF-1R and the IR in breast cancer cells. In this study, m708.5 exhibited very strong synergy with the epidermal growth factor receptor (EGFR) inhibitor gefitinib, and synergy with chemotherapeutic agents in vitro against either neuroblastoma or breast cancer cells. In xenografted models, the combination of m708.5 and gefitinib significantly inhibited LAN-1 cell growth better than single agent alone. Taken together, these results support the clinical development of m708.5 for solid tumors with potential for synergy with chemotherapy and EGFR inhibitors.

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“…In recent nanobodies have demonstrated significant translational potential in cancer therapy [ 36 ]. Nanobodies are the smallest functional antibodies which small size (~ 15 kDa) [ 37 , 38 ]. In certain conditions, there are still defects in the use of monoclonal antibodies (mAbs) in cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

Synergistic combination of targeted nano-nuclear-reactors and anti-PD-L1 nanobodies evokes persistent T cell immune activation for cancer immunotherapy

Zhu

Li²,

Guo³

et al. 2022

J Nanobiotechnol

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Background Antitumor T cell immunotherapy as a novel cancer therapeutic strategy has shown enormous promise. However, the tumor microenvironment (TME) is characterized by the low immunogenicity, hypoxia, and immunosuppressive condition that dramatically limit effective T cell immunotherapy. Thus, an ideal immunotherapy strategy that is capable of reversing the immunosuppressive TME is highly imperative. Results In this article, we reported that Fe-doped and doxorubicin (DOX) loaded HA@Cu2−XS-PEG (PHCN) nanomaterials were rationally designed as targeted Fe-PHCN@DOX nano-nuclear-reactors, which evoked persistent T cell immune response together with anti-PD-L1 nanobodies. It was confirmed that nano-nuclear-reactors displayed strong nanocatalytic effect for effective antitumor effects. Consequently, they maximized the immunogenic cell death (ICD) effect for antigen presentation and then stimulated T cell activation. In addition, Fe-PHCN@DOX could reprogram M2-phenotype tumor-associated macrophages (TAMs) into M1-phenotype TAMs by relieving tumor hypoxia. Meanwhile, blockade of the anti-PD-L1 nanobody promoted T cell activation through targeting the PD-1/PD-L1 immunosuppressive pathway. Notably, in vivo tumor therapy verified that this nano-nuclear-reactor could be used as an excellent immunotherapy nanoplatform for tumor eradication and metastasis prevention with nanobody. Conclusions Our findings demonstrated that nano-nuclear-reactors in combination with nanobody could evoke persistent T cell immune activation, suggesting them potential as a promising immunotherapy option for reversing immunosuppressive immune-cold tumors. Graphical Abstract

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A dual-specific IGF-I/II human engineered antibody domain inhibits IGF signaling in breast cancer cells

Cited by 10 publications

References 41 publications

Integrated bioinformatics analysis identifies core genes in breast cancer

Integrated bioinformatics analysis identifies core genes in breast cancer

An insulin growth factor-I/II-neutralizing monoclonal antibody in combination with epidermal growth factor receptor inhibitors potently inhibits tumor cell growth

Synergistic combination of targeted nano-nuclear-reactors and anti-PD-L1 nanobodies evokes persistent T cell immune activation for cancer immunotherapy

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