A Gelatinases‐targeting scFv‐based Fusion Protein Shows Enhanced Antitumour Activity with Endostar against Hepatoma

Gao, Ruijuan; Li, Liang; Shang, Bo-Yang; Zhao, Chunyan; Sheng, Weijin; Li, Dian-Dong

doi:10.1111/bcpt.12379

Cited by 3 publications

(4 citation statements)

References 38 publications

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“…The inhibition of these molecules could result in the suppression of these tumor development processes. Gao et al developed an anti-gelatinase scFv fused with the apoprotein, lidamidine (LDP), that when combined with Endostar, an angiogenesis inhibitor, curbed tumor growth in a xenotransplant murine model of human hepatoma [ 154 ].…”

Section: Applications Of Scfvsmentioning

confidence: 99%

Single-Chain Fragment Variable: Recent Progress in Cancer Diagnosis and Therapy

Muñoz-López

Ribas‐Aparicio

Becerra-Báez

et al. 2022

Cancers

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Cancer remains a public health problem worldwide. Although conventional therapies have led to some excellent outcomes, some patients fail to respond to treatment, they have few therapeutic alternatives and a poor survival prognosis. Several strategies have been proposed to overcome this issue. The most recent approach is immunotherapy, particularly the use of recombinant antibodies and their derivatives, such as the single-chain fragment variable (scFv) containing the complete antigen-binding domains of a whole antibody that successfully targets tumor cells. This review describes the recent progress made with scFvs as a cancer diagnostic and therapeutic tool, with an emphasis on preclinical approaches and their potential use in clinical trials.

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Section: Applications Of Scfvsmentioning

confidence: 99%

Single-Chain Fragment Variable: Recent Progress in Cancer Diagnosis and Therapy

Muñoz-López

Ribas‐Aparicio

Becerra-Báez

et al. 2022

Cancers

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“…Researchers also found that ES had an inhibitory effect on the invasion of human breast cancer cells by downregulating the expressions of MMP2 and MMP9 [18]. In other tumor fields, Gao et al [19] discovered that ES could enhance the anti-tumor activity of fusion protein in liver cancer. Thus, these studies further confirmed the role of ES in inhibiting metastasis of malignant tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Endostar blocks the metastasis, invasion and angiogenesis of ovarian cancer cells

Ding¹,

Wang²,

Cui³

et al. 2020

neo

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Endostar (ES) inhibits metastasis in some tumors, but its role in ovarian cancer invasion has not been elucidated. In this study, the effects of ES on ovarian cancer cells were further analyzed, to excavate an effective strategy for treating ovarian cancer. Ovarian cancer cell lines (SKOV3 and HO-8910PM) were treated with different concentrations of ES. Cell activity and half-maximal inhibitory concentration (IC50) detected by MTT were used for subsequent experiments. The migration and invasion abilities of treated cells were detected by wound healing and Transwell assays. The expressions of epithelialmesenchymal transition (EMT)-related proteins in treated cells were determined by western blot analysis. Moreover, in vitro angiogenesis, the expressions of related proteins in treated cells and STAT3, and PD-L1 expressions were determined. We found that with the increase of ES concentrations, the cell activity showed a decreasing trend, and that the compositive IC50 of SKOV3 and HO-8910PM was 50 μg/ml. Moreover, ES observably inhibited migration, invasion, and EMT of ovarian cancer cell lines. In angiogenesis experiments, the angiogenesis ability and the expressions of related proteins in ovarian cancer cell lines were downregulated after ES treatment. Furthermore, ES reduced the expression of PD-L1 and suppressed the phosphorylation of STAT3 in ovarian cancer cell lines. ES blocked the metastasis, invasion, and angiogenesis of ovarian cancer cells by suppressing the activation of PD-L1 and STAT3, which might be considered as the potential mechanism of ES in the treatment of ovarian cancer.

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“…Antibody-drug conjugates already show its efficacy in cancer therapy in clinic, there are more than two antibody-drug conjugates already approved by US FDA until now. To improve the antitumor efficacy of lidamycin, antibody conjugated of lidamycin seems to be a reasonable approach to further improve the efficacy of lidamycin whereas lower the side effects after systemic intravenous injection, it was documented that antibody or its fragments conjugated with lidamycin showed improved antitumor efficacy as compared to lidamycin alone 3 - 5 .…”

Section: Introductionmentioning

confidence: 99%

“…It was reported that gelatianses were related with the prognosis and microvessel density (MVD) in patients with pancreatic cancer, and would be a potential target for cancer therapy 6 , 7 . Antibody against gelatinases had been developed and the conjugation of scFv against gelatinases with lidamycin already showed potent antitumor efficacy in several kinds of cancer types, such as lung cancer, hepatoma 5 , 8 , 9 . In this study, the antitumor efficacy of scFv-based fusion protein against gelatianses conjugated with lidamycin was investigated in pancreatic cancer.…”

Section: Introductionmentioning

confidence: 99%

An arginine-rich cell penetrating peptide contained anti-gelatinase scFv-LDM fusion protein shows potent antitumor efficacy in pancreatic cancer

Zhong

Yang

et al. 2018

J. Cancer

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Pancreatic cancer (PC) is one of the most dangerous cancers with less than 5% survival rate in 5 years. This study was to evaluate the antitumor activities of dFv-LDP-AE and dFv-R-LDP-AE, two energized fusion protein targeting gelatinases, on pancreatic cancer. The fusion protein dFv-LDP-AE consists of two tandem anti-gelatianses scFv and an enediyne antibiotic lidamycin (LDM) for receptor binding and cell killing. To improve the penetration capability, the fusion protein dFv-LDP-AE was integrated with an arginine-rich cell penetrating peptide (Arg)9 and then generated the fusion protein dFv-R-LDP-AE. The current study demonstrated that dFv-LDP and dFv-R-LDP had high affinity with the antigen gelatinases and PC cells, the integration of (Arg)9 could increase the penetration rate of fusion protein in SW-1990 and PANC-1 cells. After enediyne-energized with chromophore of lidamycin, the energized fusion protein dFv-LDP-AE and dFv-R-LDP-AE showed potent cytotoxicity to PC cells and could induced the robust cell apoptosis and necrosis in vitro. Western blot showed that dFv-R-LDP-AE could increase PARP cleavage, and inhibited the expression of VEGF, Cyclin D1, Cox-2 and Bcl-2 in SW-1990 and PANC-1 cells. In vivo, at a tolerated dosage, dFv-LDP, dFv-LDP-AE and dFv-R-LDP-AE inhibited tumor growth by 20.42%, 56.31% (P < 0.01, compared to that of control) and 74.2% (P < 0.05, compared to that of dFv-LDP-AE) in pancreatic cancer SW-1990 xenografted mice, respectively. Moreover, the results of in vivo optical imaging showed that fusion protein dFv-R-LDP displayed prominent accumulation in the tumor in SW-1990 xenografted mice and Capan-2 orthotopic transplanted mice. These results showed that dFv-R-LDP-AE possessed potent antitumor efficacy on PC, which indicating it could be a promising candidate for targeting therapy of PC.

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A Gelatinases‐targeting scFv‐based Fusion Protein Shows Enhanced Antitumour Activity with Endostar against Hepatoma

Cited by 3 publications

References 38 publications

Single-Chain Fragment Variable: Recent Progress in Cancer Diagnosis and Therapy

Single-Chain Fragment Variable: Recent Progress in Cancer Diagnosis and Therapy

Endostar blocks the metastasis, invasion and angiogenesis of ovarian cancer cells

An arginine-rich cell penetrating peptide contained anti-gelatinase scFv-LDM fusion protein shows potent antitumor efficacy in pancreatic cancer

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