Binding characterization of the targeting drug AIMPILA to AFP receptors in human tumor xenografts

Tcherkassova, Janneta; Цуркан, С А; Smirnova, G. P.; Borisova, Julia; Moro, Ricardo; Treshalina, H. M.

doi:10.1177/1010428317734815

Cited by 6 publications

(9 citation statements)

References 25 publications

(52 reference statements)

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“…Because fragment AIFs, such as rAFP3D, recognize and bind to AFP receptors on the membranes of cancer cells, they transport drugs into the cell through receptor-mediated endocytosis, which increases the intake of drugs and enhances the accumulation of drugs, allowing the drugs to exert their cytotoxic effects. For example, rAFP3D conjugated to Dox (rAFP3D-G2-Dox) increases the sensitivity of human ovarian carcinoma cells, breast cancer cells and other cancer cells to Dox ( Godovannyi et al, 2011 ; Yabbarov et al, 2013 ; Tcherkassova et al, 2017 ).…”

Section: Design Of Aifs From Afp Domain-3 and Applications For Targeting Deliver Drugs To Cancer Cellsmentioning

confidence: 99%

“…Based on the origin, the types of AFP include natural AFP (nAFP), which is derived from fetal cells, and tumor-derived AFP (tAFP), which is highly expressed in HCC and other cancers. The forms of AFP are also categorized as secreted AFP (SeAFP) and cytoplasmic AFP (CyAFP) ( Mizejewski, 2015a ; Tcherkassova et al, 2017 ). Here, AFP mainly refers to tAFP, and CyAFP refers to cytoplasmic tAFP.…”

Section: Introductionmentioning

confidence: 99%

“…GIP does not bind the AFP receptor (AFPR), but it can enter the cells influence the enzyme activity of tumor cells ( Mizejewski and Butterstein, 2006 ; Mizejewski et al, 2010 ). Other new peptides of AIF could be obtained from AFP domain-3, and these peptides can bind to AFPR or signal transduction molecules and serve as candidate decoy ligands to prevent malignancy mediated by AFP ( Mizejewski, 2011b ; Tcherkassova et al, 2017 ). Fragment AIFs include AFP-3BC, rAFP3D, and r3dAFP, which are fragments of protein derived from AFP domain-3, and they can deliver drugs and be endocytosed by cancer cells with high AFPR expression ( Godovannyi et al, 2011 ; Posypanova et al, 2013 ; Yabbarov et al, 2013 ; Tcherkassova et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

“…Other new peptides of AIF could be obtained from AFP domain-3, and these peptides can bind to AFPR or signal transduction molecules and serve as candidate decoy ligands to prevent malignancy mediated by AFP ( Mizejewski, 2011b ; Tcherkassova et al, 2017 ). Fragment AIFs include AFP-3BC, rAFP3D, and r3dAFP, which are fragments of protein derived from AFP domain-3, and they can deliver drugs and be endocytosed by cancer cells with high AFPR expression ( Godovannyi et al, 2011 ; Posypanova et al, 2013 ; Yabbarov et al, 2013 ; Tcherkassova et al, 2017 ). The unique AIF, rhAFP is full-length AFP that is expressed in E. coli and in yeast cells ( Arshad et al, 2015 ), and they can also be designed as candidate decoy ligands to deliver drugs to prevent AFP malignant behaviors.…”

Section: Introductionmentioning

confidence: 99%

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AFP-Inhibiting Fragments for Drug Delivery: The Promise and Challenges of Targeting Therapeutics to Cancers

Lin

Wang

et al. 2021

Front. Cell Dev. Biol.

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Alpha fetoprotein (AFP) plays a key role in stimulating the growth, metastasis and drug resistance of hepatocellular carcinoma (HCC). AFP is an important target molecule in the treatment of HCC. The application of AFP-derived peptides, AFP fragments and recombinant AFP (AFP-inhibiting fragments, AIFs) to inhibit the binding of AFP to intracellular proteins or its receptors is the basis of a new strategy for the treatment of HCC and other cancers. In addition, AIFs can be combined with drugs and delivery agents to target treatments to cancer. AIFs conjugated to anticancer drugs not only destroy cancer cells with these drugs but also activate immune cells to kill cancer cells. Furthermore, AIF delivery of drugs relieves immunosuppression and enhances chemotherapy effects. The synergism of immunotherapy and targeted chemotherapy is expected to play an important role in enhancing the treatment effect of patients with cancer. AIF delivery of drugs will be an available strategy for the targeted treatment of cancer in the future.

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Section: Design Of Aifs From Afp Domain-3 and Applications For Targeting Deliver Drugs To Cancer Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

AFP-Inhibiting Fragments for Drug Delivery: The Promise and Challenges of Targeting Therapeutics to Cancers

Lin

Wang

et al. 2021

Front. Cell Dev. Biol.

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“…Massive necrosis can occur with high doses of atractylosides, while apoptosis can occur with low doses of atractylosides (30). Therefore, the atractyloside is used as an apoptosis inducer in animal model of tumor (31). The acquired drug resistance hampers the efficacy of chemotherapy and immunotherapy, which are appeared in the treatment of osteosarcoma (32,33) and malignant melanoma (34).…”

Section: Discussionmentioning

confidence: 99%

Atractyloside targets cancer-associated fibroblasts and inhibits the metastasis of colon cancer

et al. 2020

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Background: Several evidences have proved that cancer-associated fibroblasts (CAFs) play a crucial role in tumor progression. In fact, CAFs form a major component of tumor microenvironment (TME). Therefore, the development and metastasis of tumors can be effectively inhibited by small molecular compounds that target CAFs.Methods: In this study, we mainly analyzed the expression profile of colon cancer (CC). We determined the intensity of CAFs in CC tissues by using the immune cell infiltration score. Gene enrichment analysis and the screening of differentially expressed genes were performed on the basis of the intensity of CAFs in CC tissues. We screened the small molecular compounds that were converted from differentially expressed genes. The results indicated that atractyloside was a small molecular compound related to CAFs in CC tissues. We identified the relationship between atractylosides and CAFs through target protein analysis and network analysis, and verified the inhibition effect of atractylosides on CC cells (CCC) by migration assay and scratch wound-healing assays.Results: We found that many target proteins of atractyloside, such as the matrix metalloproteinase family and integrin proteins, were related to the biological function of CAFs. By performing network analysis, we found that the target proteins FGF1, ITGB1, and EDNRA were closely related to tumor angiogenesis, while the target proteins MMP9 and ITGAV were correlated to an extracellular matrix (ECM) and cell motility.These findings which further confirmed the relationship between atractylosides and CAFs. In addition, transwell cell migration and scratch wound-healing assays proved that atractylosides could significantly inhibit the migration of CCCs. Conclusions:The atractyloside might be a small molecular compound that potentially targets CAFs and inhibits the development as well as metastasis of CC by changing the TME.

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High anti-tumor activity of a novel alpha-fetoprotein-maytansinoid conjugate targeting alpha-fetoprotein receptors in colorectal cancer xenograft model

Griffin¹,

Hill²,

Rossi

et al. 2023

Cancer Cell Int

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The alpha-fetoprotein receptor (AFPR) is a novel target for cancer therapeutics. It is expressed on most cancers and myeloid derived suppressor cells (MDSCs) but generally absent on normal tissues. Studies were performed to investigate the use of recombinant human AFP (ACT-101) conjugated with maytansinoid toxins for targeted toxin delivery to cancer. Four structurally different ACT-101-maytansinoid conjugates containing cleavable glutathione sensitive linkers were initially investigated in a mouse xenograft model of colorectal cancer. Reduction in tumor volume was seen for all four conjugates compared to control (p < 0.05). The anti-tumor effects of the conjugate selected for further development (ACT-903) persisted after treatment discontinuation, with tumors becoming undetectable in 9 of 10 mice, and all 10 mice surviving through Day 60 with no obvious signs of toxicity. A follow-up study performed in the same model compared the effects of single intravenous doses of ACT-903 (10–50 mg/kg) to that of control groups receiving vehicle or ACT-101. A significant reduction of tumor burden compared to control was achieved in the 40 and 50 mg/kg dose groups. Survival was significantly prolonged in these 2 groups (40 mg/kg (p < 0.0001); 50 mg/kg (p = 0.0037). Free maytansine blood levels at 4 h were 0.008% of the dose, indicating stability of the conjugate in circulation as was expected based on in vitro plasma stability studies. No obvious signs of toxicity were seen in any of the treated groups. Observed efficacy and excellent tolerability of ACT-903 in these xenograft models support advancing the development of ACT-903 toward clinical use.

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Binding characterization of the targeting drug AIMPILA to AFP receptors in human tumor xenografts

Cited by 6 publications

References 25 publications

AFP-Inhibiting Fragments for Drug Delivery: The Promise and Challenges of Targeting Therapeutics to Cancers

AFP-Inhibiting Fragments for Drug Delivery: The Promise and Challenges of Targeting Therapeutics to Cancers

Atractyloside targets cancer-associated fibroblasts and inhibits the metastasis of colon cancer

High anti-tumor activity of a novel alpha-fetoprotein-maytansinoid conjugate targeting alpha-fetoprotein receptors in colorectal cancer xenograft model

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