scholarly journals Targeting multidrug resistant tumor cells with a recombinant single-chain FV fragment directed to P-glycoprotein

2001 ◽  
Vol 94 (6) ◽  
pp. 864-872 ◽  
Author(s):  
Revital Niv ◽  
Yehuda G. Assaraf ◽  
Dina Segal ◽  
Esther Pirak ◽  
Yoram Reiter
1997 ◽  
Vol 272 (47) ◽  
pp. 29784-29789 ◽  
Author(s):  
Flip J. Hoedemaeker ◽  
Tara Signorelli ◽  
Kathy Johns ◽  
Douglas A. Kuntz ◽  
David R. Rose

2021 ◽  
Vol 17 (3) ◽  
pp. 447-455
Author(s):  
Ling Ni ◽  
You-Xin Li

Purpose: Although monoclonal antibodies are used to decorate nanoparticles to target specific cells, penetration of tumor tissues by monoclonal antibodies is limited by their large size. Therefore, we prepared DM1 nanoparticles decorated with the small anti-HER2 single-chain Fv fragment (scFvHER2) of trastuzumab (TMAB) for targeting to human epidermal growth factor receptor 2 (HER2) overexpressing in breast cancer effectively. Methods: ScFvHER2 fragment was coupled with DM1 nanoparticles (NPs) via covalent thiol-maleimide linkages. Their physicochemical properties, uptake by cells, and toxicity to tumor cells were investigated. Their vivo biodistribution was assessed employing liquid chromatographytandem mass spectrometry, while their antitumor activity was investigated in nude mice burdened with BT-474 tumor. Results: Viability of BT-474 cells incubated with scFvHER2-DM1-Nanoparticles (scFv-DM1-NPs) was significantly lower than that of BT-474 cell treated with TMAB-DM1-Nanoparticles (TMAB-DM1-NPs) (P < 0 05). Uptake by cells of scFvDM1-NPs was significantly higher than TMAB-DM1-NPs (P < 0 01). Accumulation of scFv-DM1-NPs in tumor tissue was notably higher than TMAB-DM1-NPs (P < 0 05). scFv-DM1-NPs exhibited improved antitumor effects compared to TMABDM1-NPs (P < 0 05), showing a tumor inhibition rate of more than 70%. Conclusions: ScFvHER2 fragment could serve as a more effective targeting ligand than TMAB, and scFv-DM1-NPs could be developed as a possible drug delivery system to target HER2-positive breast cancer.


1997 ◽  
Vol 8 (3) ◽  
pp. 338-346 ◽  
Author(s):  
Bryan K. Cho ◽  
Edward J. Roy ◽  
Todd A. Patrick ◽  
David M. Kranz

1990 ◽  
Vol 81 (11) ◽  
pp. 1155-1161 ◽  
Author(s):  
Yuji Heike ◽  
Hirofumi Hamada ◽  
Noriaki Inamura ◽  
Saburo Sone ◽  
Takeshi Ogura ◽  
...  

2004 ◽  
Vol 315 (4) ◽  
pp. 912-918 ◽  
Author(s):  
Yasufumi Kikuchi ◽  
Shinsuke Uno ◽  
Yasushi Yoshimura ◽  
Koji Otabe ◽  
Shin-ichiro Iida ◽  
...  

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 287-287
Author(s):  
D. Xiang ◽  
Y. Ma ◽  
C. Ding ◽  
G. H. Kloecker ◽  
J. Yan

287 Background: Trastuzumab has been proven to be effective in the immunotherapy for Her-2/neu-positive breast cancer. However, this adoptively transferred therapeutic Ab must be continuously given to the patient with huge financial cost. Thus, it would be desirable if tumor vaccines could elicit long-lasting trastuzumab-like Ab. Methods: Constructing fusion protein of anti-mouse CD19 single chain variable fragment (anti-CD19-scFv) with human Her-2/neu extracellular domain P3-4 (P3-4) by extracting total RNA from Rat anti-mouse CD19 hybridoma (1D3) and first strand cDNA was synthesized accordingly. VH and VL were amplified using designed primers. Single chain Fv (VL-VH) was then synthesized by overlapping PCR. Then constructs were sequenced and cloned into pET-20b(+) vectors. Fragments P3-4 of extracellular domains of human Her-2/neu was cloned from pcDNA3.1-Her2 and then cloned into pET-20b(+)-scFv. Series of constructs were expressed and purified according to standard protocol and verified by Western Blot. Results: Both in vitro and in vivo studies demonstrated that fusion proteins anti-CD19-scFv and anti-CD19-scFv-P3-4 but not P3-4 could specifically bind to B cells with high affinity. Mice immunized with anti-CD19-scFv-P3-4 secreted higher titers of IgG and IgM than those from controls (p<0.05). Studies also demonstrated that sera from anti-CD19-scFv-P3-4 but not anti-CD19-scFv or P3-4 immunized mice stained with Her-2/neu expressing SKOV-3 tumor cells. These Abs also competitively inhibited trastuzumab-mediated Ag binding, suggesting that trastuzumab-like Ab responses were elicited. WT mice immunized with anti-CD19-scFv-P3-4 fusion protein then challenged with D2/F2-Her-2 mammary tumor cells showed significantly reduced tumor burden compared to those immunized with control fusion proteins (p<0.05) and had enhanced median overall survival to 45 days versus 34 days in WT mice immunized with either anti-CD19-scFv or P3-4. Conclusions: Targeting of Her-2/neu antigens to B cells stimulates Th-dependent humoral immune responses with anti tumor effect in mouse model. These findings provide a novel avenue for successful development of breast cancer vaccination strategy and help to fight for cancer.


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