Tumor targeting in a murine tumor xenograft model with the (sFv′)2 divalent form of anti-c-erbB-2 single-chain Fv

1994 ◽  
Vol 24-25 (1-3) ◽  
pp. 267-278 ◽  
Author(s):  
James S. Huston ◽  
Gregory P. Adams ◽  
John E. McCartney ◽  
Mei-Sheng Tai ◽  
Robert M. Hudziak ◽  
...  
Keyword(s):  
Tumor Targeting ◽  
Xenograft Model ◽  
Tumor Xenograft ◽  
Single Chain ◽  
Murine Tumor ◽  
Single Chain Fv

Corrigendum to “Tumor-targeting CTL expressing a single-chain Fv specific for VEGFR2” [Biochem. Biophys. Res. Commun. 394 (2010) 54–58]

2012 ◽  
Vol 417 (3) ◽  
pp. 1106
Author(s):  
Naoko Kanagawa ◽  
Tatsuya Yanagawa ◽  
Yohei Mukai ◽  
Yasuo Yoshioka ◽  
Naoki Okada ◽  
...  
Keyword(s):  
Tumor Targeting ◽  
Single Chain ◽  
Single Chain Fv

scholarly journals Engineered Fragments of the PSMA-Specific 5D3 Antibody and Their Functional Characterization

2020 ◽  
Vol 21 (18) ◽  
pp. 6672
Author(s):  
Zora Novakova ◽  
Nikola Belousova ◽  
Catherine A. Foss ◽  
Barbora Havlinova ◽  
Marketa Gresova ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Xenograft Model ◽  
In Vitro Assays ◽  
Experimental Therapy ◽  
Single Chain ◽  
Single Chain Fv ◽  
Murine Xenograft Model ◽  
Single Target

Prostate-Specific Membrane Antigen (PSMA) is an established biomarker for the imaging and experimental therapy of prostate cancer (PCa), as it is strongly upregulated in high-grade primary, androgen-independent, and metastatic lesions. Here, we report on the development and functional characterization of recombinant single-chain Fv (scFv) and Fab fragments derived from the 5D3 PSMA-specific monoclonal antibody (mAb). These fragments were engineered, heterologously expressed in insect S2 cells, and purified to homogeneity with yields up to 20 mg/L. In vitro assays including ELISA, immunofluorescence and flow cytometry, revealed that the fragments retain the nanomolar affinity and single target specificity of the parent 5D3 antibody. Importantly, using a murine xenograft model of PCa, we verified the suitability of fluorescently labeled fragments for in vivo imaging of PSMA-positive tumors and compared their pharmacokinetics and tissue distribution to the parent mAb. Collectively, our data provide an experimental basis for the further development of 5D3 recombinant fragments for future clinical use.

scholarly journals Tumor Targeting by a Multivalent Single-Chain Fv (scFv) Anti-Lewis Y Antibody Construct

2008 ◽  
Vol 23 (4) ◽  
pp. 411-424 ◽  
Author(s):  
Marcus P. Kelly ◽  
F.-T. Lee ◽  
Kiki Tahtis ◽  
Barbara E. Power ◽  
Fiona E. Smyth ◽  
...  
Keyword(s):  
Tumor Targeting ◽  
Single Chain ◽  
Single Chain Fv ◽  
Lewis Y

HM1.24/CD317-directed immunotoxin to eliminate malignant plasma cells in vitro and in vivo.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8604-8604
Author(s):  
Martin Gramatzki ◽  
Matthias Staudinger ◽  
Pia Glorius ◽  
Katja Klausz ◽  
Christian Kellner ◽  
...  
Keyword(s):  
Mouse Model ◽  
Plasma Cells ◽  
Xenograft Model ◽  
Clinical Activity ◽  
Target Structure ◽  
Single Chain ◽  
Pseudomonas Exotoxin A ◽  
Single Chain Fv

8604 Background: Targeted immunotherapy, based on antibodies against tumor-associated antigens, is a promising approach for the treatment of multiple myeloma (MM). Recently, antibody-based strategies delivering a toxic payload have documented impressive clinical activity in hematological malignancies. In particular, surface molecules overexpressed on malignant plasma cells and efficiently internalized represent promising targets for developing myeloma-directed immunoconstructs. Here, the identification of CD317 (HM1.24) as a potent target structure and the characterization of a novel CD317-directed single-chain immunotoxin, HM1.24-ETA', is described. Methods: Using a novel screening tool, a panel of antibodies against MM-associated antigens was evaluated for their ability to mediate antigen-dependent delivery of a truncated version of Pseudomonas exotoxin A (ETA’) to MM cells. HM1.24-ETA' was generated by genetic fusion of a CD317-specific single-chain Fv antibody and ETA'. The anti-myeloma activity of the E. coli-expressed immunotoxin was evaluated in vitro and in a xenograft mouse model. Results: By screening a panel of antibodies including CD38, CS1, IL-6R, CD138 and CD317, CD317 was identified as a suitable receptor to deliver ETA’ to MM cells. The subsequently designed recombinant HM1.24-ETA' immunotoxin efficiently inhibited growth of MM cell lines with halfmaximal growth inhibition at concentrations of less than 1 nM. Antigen-specific MM cell killing occurred via induction of apoptosis. The proliferation of IL-6 dependent INA-6 cells was completely inhibited by HM1.24-ETA' even in the presence of bone marrow stromal cells that otherwise strongly support tumor cell growth. Importantly, HM1.24-ETA' strongly triggered apoptosis (up to 80%) in freshly isolated tumor cells from 7 out of 7 MM patients. In a xenograft SCID mouse model, establishment of INA-6 plasma cell tumors was efficiently abrogated by treatment with HM1.24-ETA' immunotoxin (p < 0.04). Conclusions: The HM1.24-ETA' immunotoxin in vitro and in the preclinical xenograft model in vivo demonstrates that the CD317 antigen may represent a promising target structure for immunotherapy of MM using immunoconjugates with toxic payloads.

Determinants of selective tumor targeting by single-chain Fv molecules

1996 ◽  
Vol 2 (1) ◽  
pp. 73
Author(s):  
L.M. Weiner ◽  
J. Marks ◽  
J. Huston ◽  
R. Schierb ◽  
J. McCartney ◽  
...  
Keyword(s):  
Tumor Targeting ◽  
Single Chain ◽  
Single Chain Fv

Tumor-targeting CTL expressing a single-chain Fv specific for VEGFR2

2010 ◽  
Vol 394 (1) ◽  
pp. 54-58 ◽  
Author(s):  
Naoko Kanagawa ◽  
Tatsuya Yanagawa ◽  
Yohei Mukai ◽  
Yasuo Yoshioka ◽  
Naoki Okada ◽  
...  
Keyword(s):  
Tumor Targeting ◽  
Single Chain ◽  
Single Chain Fv

Generating improved single-chain Fv molecules for tumor targeting

1999 ◽  
Vol 231 (1-2) ◽  
pp. 249-260 ◽  
Author(s):  
Gregory P Adams ◽  
Robert Schier
Keyword(s):  
Tumor Targeting ◽  
Single Chain ◽  
Single Chain Fv

scholarly journals Production and Characterization of a Humanized Single-chain Antibody against Human Integrin αvβ3 Protein

2011 ◽  
Vol 286 (27) ◽  
pp. 24500-24507 ◽  
Author(s):  
Dabin Liu ◽  
Chen Wang ◽  
Cun Li ◽  
Xin Zhang ◽  
Baozhong Zhang ◽  
...  
Keyword(s):  
Xenograft Model ◽  
Integrin Αvβ3 ◽  
Soluble Form ◽  
Tumor Type ◽  
Single Chain ◽  
Single Chain Antibody ◽  
Form Analysis ◽  
Phage Antibodies ◽  
Single Chain Fv ◽  
Human Integrin

Anti-angiogenesis therapy is an emerging strategy for cancer treatment. This therapy has many advantages over existing treatments, such as fewer side effects, fewer resistance problems, and a broader tumor type spectrum. Integrin αvβ3 is a heterodimeric transmembrane glycoprotein that has been demonstrated to play a key role in tumor angiogenesis and metastasis. We have used a phage antibody display to humanize a mouse monoclonal antibody (mAb E10) against human integrin αvβ3 with a predetermined CDR3 gene. Three human phage antibodies were developed. Analysis of the humanized phage antibodies by phage ELISA revealed that the antibodies retained high antigen-binding activity and detected the same epitope as the parent mAb E10. A humanized single chain Fv (scFv) antibody was expressed in Escherichia coli in a soluble form. Analysis of the purified scFv indicated that it has the same specificity and affinity as the original mAb. Cell viability assays and xenograft model results suggested that the humanized scFv possesses anti-tumor growth activity in vitro and in vivo. This successful production of a humanized scFv with the ability to inhibit αvβ3-mediated cancer cell growth may provide a novel candidate for integrin αvβ3-targeted therapy.

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