A tandem scFv-based fusion protein and its enediyne-energized analogue show intensified therapeutic efficacy against lung carcinoma xenograft in athymic mice

Zhong, Genshen; Zhang, Shenghua; Li, Yang; Liu, Xiujun; Gao, Ruijuan; Qin, Miao; Zhen, Yong‐Su

doi:10.1016/j.canlet.2010.02.020

Cited by 28 publications

(46 citation statements)

References 28 publications

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“…The preparation of the dFv-LDP fusion protein and its enediyne-energized product dFv-LDP-AE were described in our previous report (15). MTT and FITC were purchased from Sigma Chemical Co. (USA).…”

Section: Methodsmentioning

confidence: 99%

“…Control nude mice were injected with saline. Tumor growth was measured with a caliper, and tumor volumes were calculated with the following formula: V=0.5a x b 2 , where a and b are the long and the perpendicular short diameters of the tumor, respectively (15). The data are presented as the mean ± SD.…”

Section: Binding Specificity Of Dfv-ldp With Cancer Cells By Immunoflmentioning

confidence: 99%

“…After purification and refolding as reported previously (15). In this study, the PAGE was used to analyze the fusion protein dFv-LDP under reduced and nonreduced conditions.…”

Section: The Preparation Of Dfv-ldp Fusion Proteinmentioning

confidence: 99%

“…It has been documented that antibody-lidamycin conjugate showed very good antitumor efficacy in vitro and in vivo (12)(13)(14). Our previous results demonstrated that a tandem scFv format conjugated with lidamycin (dFv-LDP-AE) improved the antitumor efficacy compared with the scFv-lidamycin conjugate, and showed excellent tumor targeting capability to certain Antitumor activities of dFv-LDP-AE: An enediyne-energized fusion protein targeting tumor-associated antigen gelatinases tumor cell lines, which indicated that the dFv-LDP-AE is a promising anticancer agent for development (15). As HCC is a leading cause of cancer death in China, developing new therapeutic strategies is warranted.…”

Section: Introductionmentioning

confidence: 99%

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Antitumor activities of dFv-LDP-AE: An enediyne-energized fusion protein targeting tumor-associated antigen gelatinases

Zhong

Guo

et al. 2012

Oncology Reports

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Abstract.Gelatinases play an important role in tumor growth and metastasis, and overexpression of these molecules is strongly correlated with poor prognosis in a variety of malignant tumors. Lidamycin is an enediyne antitumor antibiotic with potent cytotoxicity. We previously reported that a tandem scFv format (dFv-LDP-AE) showed enhanced binding ability with gelatinases compared with the scFv-lidamycin conjugate (Fv-LDP-AE). In this study, the antitumor activities of dFv-LDP-AE on hepatocellular carcinoma (HCC) were evaluated in vitro and in vivo. By SDS-PAGE analysis, it was found that partial fusion protein dFv-LDP existed as dimer; the results of ELISA and immunofluorescence demonstrated that the fusion protein dFv-LDP could efficiently bind to hepatoma cells in vitro. The apparent arrest of cell cycle at G2/M phase and induction of apoptosis at nanomole levels indicated that the dFv-LDP-AE was very potent against HCC. In in vivo experiments, dFv-LDP-AE shown enhanced cytotoxic effects compared to those of LDM. Administration at mouse tolerable dosage level, the inhibition rate of tumor growth was 89.5% of dFv-LDP-AE vs. 73.6% of LDM on transplantable H22 in mice (P<0.05) and, 87.3% of dFv-LDP-AE vs. 63.4% of LDM on hepatoma Bel-7402 in athymic mice (P<0.01). Small animal optical imaging showed that the FITC-labeled dFv-LDP preferentially localized in the tumor site in less than 30 min, which demonstrated remarkable tumor-targeting properties. Taken together with the above findings, the enediyne-energized fusion protein dFv-LDP-AE showed potential application as a new agent for therapeutic appications in HCC.

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Section: Methodsmentioning

confidence: 99%

Section: Binding Specificity Of Dfv-ldp With Cancer Cells By Immunoflmentioning

confidence: 99%

“…After purification and refolding as reported previously (15). In this study, the PAGE was used to analyze the fusion protein dFv-LDP under reduced and nonreduced conditions.…”

Section: The Preparation Of Dfv-ldp Fusion Proteinmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Antitumor activities of dFv-LDP-AE: An enediyne-energized fusion protein targeting tumor-associated antigen gelatinases

Zhong

Guo

et al. 2012

Oncology Reports

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“…The combined extracts were washed with brine, dried (MgSO 4 ) and concentrated in vacuo to provide 9.11 g (53%) of compound 9: Animal experiments. Antitumor activity using A549 xenograft nude mice: [10][11][12] BALB/c-nu Slc mice (5 -6 weeks old) were purchased from Central Lab. Animal Inc. (Seoul, Korea) and were acclimatized 7 cells/mL were injected subcutaneously into dorsum region of the BALB/c-nu Slc mice and the tumors were allowed to grow.…”

Section: Introductionmentioning

confidence: 99%

Anti-Cancer Activity of T-Type Calcium Channel Blocker In Vivo

Park¹,

Jung²,

Lee³

et al. 2010

Bulletin of the Korean Chemical Society

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3,4-Dihydroquinazoline 1 as T-type calcium channel blocker was in vivo evaluated against A549 xenograft in BALB/c-nu Slc mice, which exhibited 54% tumor growth inhibition through oral administration of 8 mg/kg of body weight and was slightly less active than doxorubicin (68%). In addition, this compound was also profiled for its acute toxicity to ICR mice to afford oral LD50 value of 1,038 mg/kg of body weight.

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A novel enediyne‐integrated antibody–drug conjugate shows promising antitumor efficacy against CD30⁺ lymphomas

Wang

Zhang

et al. 2018

Molecular Oncology

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CD30 is a 120‐kDa type I transmembrane glycoprotein belonging to the tumor necrosis factor receptor superfamily. Overexpression of CD30 has been reported in Hodgkin's lymphoma (HL) and anaplastic large‐cell lymphoma (ALCL). CD30‐targeted treatment with antibody–drug conjugates (ADCs) can lead to promising clinical benefit. Lidamycin (LDM), consisting of an apoprotein LDP and an active enediyne chromophore AE, is a member of the enediyne antibiotic family and one of the most potent antitumor agents. AE and LDP can be dissociated and reconstituted under certain conditions in vitro. LDM is an ideal payload for the preparation of ADCs. In this study, we show the generation, production, and antitumor activity of anti‐CD30‐LDM, a novel ADC which consists of the intact anti‐CD30 antibody and LDM. First, the anti‐CD30‐LDP fusion protein was constructed and expressed in CHO/dhFr− cells. Anti‐CD30‐LDP showed specific and high‐affinity binding to CD30 and could be internalized into target cells. It also exhibited excellent tumor‐targeting capability in vivo. Next, anti‐CD30‐LDM was prepared by assembling the enediyne molecule AE to the fusion protein anti‐CD30‐LDP. Anti‐CD30‐LDM was highly cytotoxic to HL and ALCL cell lines, with IC50 values of 5–50 pm. It can also induce cell apoptosis and G2/M cell cycle arrest. In the Karpas299 xenograft model, the tumor growth was inhibited by 87.76% in mice treated with anti‐CD30‐LDM and with no discernible adverse effects. Taken together, anti‐CD30‐LDM shows attractive tumor‐targeting capability and antitumor efficacy both in vitro and in vivo and could be a promising candidate for the treatment of CD30+ lymphomas.

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A tandem scFv-based fusion protein and its enediyne-energized analogue show intensified therapeutic efficacy against lung carcinoma xenograft in athymic mice

Cited by 28 publications

References 28 publications

Antitumor activities of dFv-LDP-AE: An enediyne-energized fusion protein targeting tumor-associated antigen gelatinases

Antitumor activities of dFv-LDP-AE: An enediyne-energized fusion protein targeting tumor-associated antigen gelatinases

Anti-Cancer Activity of T-Type Calcium Channel Blocker In Vivo

A novel enediyne‐integrated antibody–drug conjugate shows promising antitumor efficacy against CD30⁺ lymphomas

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A tandem scFv-based fusion protein and its enediyne-energized analogue show intensified therapeutic efficacy against lung carcinoma xenograft in athymic mice

Cited by 28 publications

References 28 publications

Antitumor activities of dFv-LDP-AE: An enediyne-energized fusion protein targeting tumor-associated antigen gelatinases

Antitumor activities of dFv-LDP-AE: An enediyne-energized fusion protein targeting tumor-associated antigen gelatinases

Anti-Cancer Activity of T-Type Calcium Channel Blocker In Vivo

A novel enediyne‐integrated antibody–drug conjugate shows promising antitumor efficacy against CD30+ lymphomas

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A novel enediyne‐integrated antibody–drug conjugate shows promising antitumor efficacy against CD30⁺ lymphomas