Correction: Serwotka-Suszczak, A. M. et al. A Conjugate Based on Anti-HER2 Diaffibody and Auristatin E Targets HER2-Positive Cancer Cells. Int. J. Mol. Sci. 2017, 18, 401

Serwotka-Suszczak, Anna; Sochaj-Gregorczyk, Alicja; Pieczykolan, Jerzy; Krowarsch, Daniel; Jeleń, Filip; Otlewski, Jacek

doi:10.3390/ijms19113676

Cited by 1 publication

(1 citation statement)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Conjugates and genetic fusions between small, engineered, non-antibody domains that bind tumor-associated targets and cytotoxic payloads have been described previously ( Martin-Killias et al , 2011 ; Simon et al , 2013 ; Cox et al , 2016 ; Currier et al , 2016 ; Goldberg et al , 2016 ; Sochaj-Gregorczyk et al , 2016 , 2017 ; Serwotka-Suszczak et al , 2017 ; Sokolova et al , 2017 ). In contrast to the conjugates described here, the majority of the previously reported scaffold–drug conjugates that have been tested in animal models had been modified to extend their naturally short half-life to approximate the pharmacokinetics of antibodies, with the goal of maximizing exposure of tumors to the cytotoxic payloads and thus maximizing efficacy.…”

Section: Introductionmentioning

confidence: 99%

Adnectin–drug conjugates for Glypican-3-specific delivery of a cytotoxic payload to tumors

Lipovšek

Carvajal

Allentoff

et al. 2018

Protein Engineering, Design and Selection

View full text Add to dashboard Cite

Tumor-specific delivery of cytotoxic agents remains a challenge in cancer therapy. Antibody–drug conjugates (ADC) deliver their payloads to tumor cells that overexpress specific tumor-associated antigens—but the multi-day half-life of ADC leads to high exposure even of normal, antigen-free, tissues and thus contributes to dose-limiting toxicity. Here, we present Adnectin–drug conjugates, an alternative platform for tumor-specific delivery of cytotoxic payloads. Due to their small size (10 kDa), renal filtration eliminates Adnectins from the bloodstream within minutes to hours, ensuring low exposure to normal tissues. We used an engineered cysteine to conjugate an Adnectin that binds Glypican-3, a membrane protein overexpressed in hepatocellular carcinoma, to a cytotoxic derivative of tubulysin, with the drug-to-Adnectin ratio of 1. We demonstrate specific, nanomolar binding of this Adnectin–drug conjugate to human and murine Glypican-3; its high thermostability; its localization to target-expressing tumor cells in vitro and in vivo, its fast clearance from normal tissues and its efficacy against Glypican-3-positive mouse xenograft models.

show abstract

Section: Introductionmentioning

confidence: 99%

Adnectin–drug conjugates for Glypican-3-specific delivery of a cytotoxic payload to tumors

Lipovšek

Carvajal

Allentoff

et al. 2018

Protein Engineering, Design and Selection

View full text Add to dashboard Cite

show abstract

Correction: Serwotka-Suszczak, A. M. et al. A Conjugate Based on Anti-HER2 Diaffibody and Auristatin E Targets HER2-Positive Cancer Cells. Int. J. Mol. Sci. 2017, 18, 401

Abstract: It has been brought to our attention that the affiliation of Dr. Jerzy Pieczykolan at the time when he was responsible for the work described in the paper [...]

Cited by 1 publication

References 1 publication

Adnectin–drug conjugates for Glypican-3-specific delivery of a cytotoxic payload to tumors

Adnectin–drug conjugates for Glypican-3-specific delivery of a cytotoxic payload to tumors

Contact Info

Product

Resources

About