Optimization of in vivo tumor targeting in SCID mice with divalent forms of 741F8 anti-c-erbB-2 single-chain Fv: effects of dose escalation and repeated i.v. administration

1995 ◽  
Vol 40 (5) ◽  
pp. 299-306 ◽  
Author(s):  
Gregory P. Adams ◽  
John E. McCartney ◽  
Ellen J. Wolf ◽  
Jamie Eisenberg ◽  
Mei-Sheng Tai ◽  
...  
1995 ◽  
Vol 40 (5) ◽  
pp. 299-306
Author(s):  
Gregory P. Adams ◽  
John E. McCartney ◽  
Ellen J. Wolf ◽  
Jamie Eisenberg ◽  
Mei-Sheng Tai ◽  
...  

2006 ◽  
Vol 12 (5) ◽  
pp. 1599-1605 ◽  
Author(s):  
Gregory P. Adams ◽  
Mei-Sheng Tai ◽  
John E. McCartney ◽  
James D. Marks ◽  
Walter F. Stafford ◽  
...  

1990 ◽  
Vol 82 (14) ◽  
pp. 1191-1197 ◽  
Author(s):  
D. Colcher ◽  
R. Bird ◽  
M. Roselli ◽  
K. D. Hardman ◽  
S. Johnson ◽  
...  

2012 ◽  
Vol 417 (3) ◽  
pp. 1106
Author(s):  
Naoko Kanagawa ◽  
Tatsuya Yanagawa ◽  
Yohei Mukai ◽  
Yasuo Yoshioka ◽  
Naoki Okada ◽  
...  

2020 ◽  
Vol 21 (18) ◽  
pp. 6672
Author(s):  
Zora Novakova ◽  
Nikola Belousova ◽  
Catherine A. Foss ◽  
Barbora Havlinova ◽  
Marketa Gresova ◽  
...  

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.


1998 ◽  
Vol 88 (12) ◽  
pp. 1367-1371 ◽  
Author(s):  
Y. D. Chen ◽  
T. A. Chen

In an attempt to develop maize plants with resistance to corn stunt spi-roplasma (CSS), a single-chain Fv fragment (scFv) gene that was constructed from antibodies with strong inhibitory activity against CSS, was expressed in a cell line of maize. However, plants regenerated from this transgenic cell line showed no distinct resistance to CSS infection under the greenhouse conditions. The affinity and functionality of scFv in vivo and the locations of CSS and expressed scFv in maize could be a part of the contributing factors affecting this result. Progress of expressing antibodies in plants for plant pathogen resistance is also discussed.


2008 ◽  
Vol 23 (4) ◽  
pp. 411-424 ◽  
Author(s):  
Marcus P. Kelly ◽  
F.-T. Lee ◽  
Kiki Tahtis ◽  
Barbara E. Power ◽  
Fiona E. Smyth ◽  
...  

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8604-8604
Author(s):  
Martin Gramatzki ◽  
Matthias Staudinger ◽  
Pia Glorius ◽  
Katja Klausz ◽  
Christian Kellner ◽  
...  

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.


2014 ◽  
Vol 186 ◽  
pp. 1-10 ◽  
Author(s):  
Ronny Rüger ◽  
Felista L. Tansi ◽  
Markus Rabenhold ◽  
Frank Steiniger ◽  
Roland E. Kontermann ◽  
...  

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