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Conditionally activ...
Conditionally activated affibody-based prodrug targeting EGFR demonstrates improved tumour selectivity
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- Leitao, Charles Dahlsson, 1992- (författare)
- KTH,Proteinvetenskap,KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Dept Prot Sci, Stockholm, Sweden.
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- Mestre Borras, Anna, 1994- (författare)
- KTH,Proteinvetenskap,KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Dept Prot Sci, Stockholm, Sweden.
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- Xu, Tianqi (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden.
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- Oroujeni, Maryam, PhD, 1982- (författare)
- Uppsala universitet,Cancerprecisionsmedicin,Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden.
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- Liu, Yongsheng (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden.
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- Westerberg, Cornelia (författare)
- KTH,Proteinvetenskap,KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Dept Prot Sci, Stockholm, Sweden.
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- Clinton, Jacob (författare)
- KTH,Proteinvetenskap,KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Dept Prot Sci, Stockholm, Sweden.
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- Tolmachev, Vladimir (författare)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Radiologi,Science for Life Laboratory, SciLifeLab,Cancerprecisionsmedicin,Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden.
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- Orlova, Anna, 1960- (författare)
- Uppsala universitet,Theranostics,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Dept Med Chem, Uppsala, Sweden.;Uppsala Univ, Sci Life Lab, S-75237 Uppsala, Sweden.
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- Ståhl, Stefan, 1961- (författare)
- KTH,Proteinvetenskap,KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Dept Prot Sci, Stockholm, Sweden.
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- Vorobyeva, Anzhelika (författare)
- Uppsala universitet,Cancerprecisionsmedicin,Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden.
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- Löfblom, John (författare)
- KTH,Proteinvetenskap,KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Dept Prot Sci, Stockholm, Sweden.
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(creator_code:org_t)
- Elsevier BV, 2023
- 2023
- Engelska.
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 357, s. 185-195
- Relaterad länk:
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Safety and efficacy of cancer-targeting treatments can be improved by conditional activation enabled by the distinct milieu of the tumour microenvironment. Proteases are intricately involved in tumourigenesis and commonly dysregulated with elevated expression and activity. Design of prodrug molecules with protease -dependent activation has the potential to increase tumour-selective targeting while decreasing exposure to healthy tissues, thus improving the safety profile for patients. Higher selectivity could also allow for adminis-tration of higher doses or use of more aggressive treatment options, leading to higher therapeutic efficacy. We have previously developed an affibody-based prodrug with conditional targeting of EGFR conferred by an anti-idiotypic affibody masking domain (ZB05). We could show that binding to endogenous EGFR on cancer cells in vitro was restored following proteolytic removal of ZB05. In this study we evaluate a novel affibody-based pro -drug design, which incorporates a protease substrate sequence recognized by cancer-associated proteases and demonstrate the potential of this approach for selective tumour-targeting and shielded uptake in healthy tissues in vivo using tumour-bearing mice. This may widen the therapeutic index of cytotoxic EGFR-targeted thera-peutics by decreasing side effects, improving selectivity of drug delivery, and enabling the use of more potent cytotoxic drugs.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- Affibody molecule
- Prodrug
- Cancer
- Conditional activation
- Tumour proteases
- Epidermal growth factor receptor
- Radionuclide imaging
- SPECT
- Targeted therapy
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- ref (ämneskategori)
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Leitao, Charles ...
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Mestre Borras, A ...
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Xu, Tianqi
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Oroujeni, Maryam ...
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Liu, Yongsheng
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Westerberg, Corn ...
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visa fler...
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Clinton, Jacob
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Tolmachev, Vladi ...
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Orlova, Anna, 19 ...
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Ståhl, Stefan, 1 ...
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Vorobyeva, Anzhe ...
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Löfblom, John
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- NATURVETENSKAP
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Kungliga Tekniska Högskolan
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Uppsala universitet