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Eriksson Karlström, AmelieORCID iD iconorcid.org/0000-0002-0695-5188
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Publications (10 of 73) Show all publications
Stiller, C., Aghelpasand, H., Frick, T., Westerlund, K., Ahmadian, A. & Eriksson Karlström, A. (2019). Fast and Efficient Fc-Specific Photoaffinity Labeling To Produce Antibody-DNA Conjugates. Bioconjugate chemistry, 30(11), 2790-2798
Open this publication in new window or tab >>Fast and Efficient Fc-Specific Photoaffinity Labeling To Produce Antibody-DNA Conjugates
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2019 (English)In: Bioconjugate chemistry, ISSN 1043-1802, E-ISSN 1520-4812, Vol. 30, no 11, p. 2790-2798Article in journal (Refereed) Published
Abstract [en]

Antibody DNA conjugates are powerful tools for DNA-assisted protein analysis. Growing usage of these methods demands efficient production of high-quality conjugates. We developed an easy and fast synthesis route yielding covalent antibody-DNA conjugates with a defined conjugation site and low batch-to-batch variability. We utilize the Z domain from protein A, containing the unnatural amino acid 4-benzoylphenylalanine (BPA) for photoaffinity labeling of the antibodies' Fc region. Z(xBPA) domains are C-terminally modified with triple-glycine (G(3))-modified DNA-oligonucleotides enzymatic Sortase A coupling. We reliable modification of the most commonly used IgG's. To prove our conjugates' functionality, we detected antibody-antigen binding events in an assay called Droplet Barcode Sequencing for Protein analysis (DBS-Pro). It confirms not only retained functionality for both conjugate parts but also the potential of using DBS-Pro for quantifying protein abundances. As intermediates are easily storable and our approach is modular, it offers a convenient strategy for screening various antibody-DNA conjugates using the same starting material.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2019
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:kth:diva-265445 (URN)10.1021/acs.bioconjchem.9b00548 (DOI)000499743100008 ()31609586 (PubMedID)2-s2.0-85074441977 (Scopus ID)
Note

QC 20191212

Available from: 2019-12-12 Created: 2019-12-12 Last updated: 2019-12-12Bibliographically approved
Cavallaro, S., Horak, J., Haag, P., Gupta, D., Stiller, C., Sahu, S. S., . . . Dev, A. (2019). Label-Free Surface Protein Profiling of Extracellular Vesicles by an Electrokinetic Sensor. ACS SENSORS, 4(5), 1399-1408
Open this publication in new window or tab >>Label-Free Surface Protein Profiling of Extracellular Vesicles by an Electrokinetic Sensor
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2019 (English)In: ACS SENSORS, ISSN 2379-3694, Vol. 4, no 5, p. 1399-1408Article in journal (Refereed) Published
Abstract [en]

Small extracellular vesicles (sEVs) generated from the endolysosomal system, often referred to as exosomes, have attracted interest as a suitable biomarker for cancer diagnostics, as they carry valuable biological information and reflect their cells of origin. Herein, we propose a simple and inexpensive electrical method for label-free detection and profiling of sEVs in the size range of exosomes. The detection method is based on the electrokinetic principle, where the change in the streaming current is monitored as the surface markers of the sEVs interact with the affinity reagents immobilized on the inner surface of a silica microcapillary. As a proof-of-concept, we detected sEVs derived from the non-small-cell lung cancer (NSCLC) cell line H1975 for a set of representative surface markers, such as epidermal growth factor receptor (EGFR), CD9, and CD63. The detection sensitivity was estimated to be similar to 175000 sEVs, which represents a sensor surface coverage of only 0.04%. We further validated the ability of the sensor to measure the expression level of a membrane protein by using sEVs displaying artificially altered expressions of EGFR and CD63, which were derived from NSCLC and human embryonic kidney (HEK) 293T cells, respectively. The analysis revealed that the changes in EGFR and CD63 expressions in sEVs can be detected with a sensitivity in the order of 10% and 3%, respectively, of their parental cell expressions. The method can be easily parallelized and combined with existing microfluidic-based EV isolation technologies, allowing for rapid detection and monitoring of sEVs for cancer diagnosis.

Place, publisher, year, edition, pages
AMER CHEMICAL SOC, 2019
Keywords
extracellular vesicles, electrokinetic effect, biosensor, label-free, protein profiling, cancer
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:kth:diva-254037 (URN)10.1021/acssensors.9b00418 (DOI)000469410100034 ()31020844 (PubMedID)2-s2.0-85066017871 (Scopus ID)
Note

Qc 20190814

Available from: 2019-08-14 Created: 2019-08-14 Last updated: 2019-08-14Bibliographically approved
Westerlund, K., Vorobyeva, A., Mitran, B., Orlova, A., Tolmachev, V., Eriksson Karlström, A. & Altai, M. (2019). Site-specific conjugation of recognition tags to trastuzumab for peptide nucleic acid-mediated radionuclide HER2 pretargeting. Biomaterials, 203, 73-85
Open this publication in new window or tab >>Site-specific conjugation of recognition tags to trastuzumab for peptide nucleic acid-mediated radionuclide HER2 pretargeting
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2019 (English)In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 203, p. 73-85Article in journal (Refereed) Published
Abstract [en]

Pretargeting is a promising strategy to reach high imaging contrast in a shorter time than by targeting with directly radiolabeled monoclonal antibodies (mAbs). One of problems in pretargeting is a site-specific, reproducible and uniform conjugation of recognition tags to mAbs. To solve this issue we propose a photoconjugation to covalently couple a recognition tag to a mAb via a photoactivatable Z domain. The Z-domain, a 58-amino acid protein derived from the IgG-binding B-domain of Staphylococcus aureus protein A, has a well-characterized binding site in the Fc portion of IgG. We tested the feasibility of this approach using pretargeting based on hybridization between peptide nucleic acids (PNAs). We have used photoconjugation to couple trastuzumab with the PNA-based hybridization probe, HP1. A complementary [Co-57]Co-labeled PNA hybridization probe ([Co-57]Co-HP2) was used as the secondary targeting probe. In vitro studies demonstrated that trastuzumab-ZHP1 bound specifically to human epidermal growth factor receptor 2 (HER2)-expressing cells with nanomolar affinity. The binding of the secondary [Co-57]Co-HP2 probe to trastuzumab-PNA-pretreated cells was in the picomolar affinity range. A two-fold increase in SKOV-3 tumor targeting was achieved when [Co-57]Co-HP2 (0.7 nmol) was injected 48 h after injection of trastuzumab-ZHP1 (0.5 nmol) compared with trastuzumab-ZHP1 alone (0.8 +/- 0.2 vs. 0.33 +/- 0.06 %ID/g). Tumor accumulation of [Co-57]Co-HP2 was significantly reduced by pre-saturation with trastuzumab or when no trastuzumab-ZHP1 was preinjected. A tumor-to-blood uptake ratio of 1.5 +/- 0.3 was achieved resulting in a clear visualization of HER2-expressing xenografts as confirmed by SPECT imaging. In conclusion, the feasibility of stable site-specific coupling of a PNA-based recognition tag to trastuzumab and successful pretargeting has been demonstrated. This approach can hopefully be used for a broad range of mAbs and recognition tags.

Place, publisher, year, edition, pages
ELSEVIER SCI LTD, 2019
Keywords
Antibody, Peptide nucleic acid, Pretargeting, Photoconjugation, Molecular imaging
National Category
Materials Engineering
Identifiers
urn:nbn:se:kth:diva-249778 (URN)10.1016/j.biomaterials.2019.02.012 (DOI)000463295600008 ()30877838 (PubMedID)2-s2.0-85063113279 (Scopus ID)
Note

QC 20190429

Available from: 2019-04-29 Created: 2019-04-29 Last updated: 2019-04-29Bibliographically approved
Altai, M., Vorobyeva, A., Westerlund, K., Mitran, B., Orlova, A., Eriksson Karlström, A. & Tolmachev, V. (2018). A novel method for conjugation of PNA to antibodies for radionuclide based pretargeting: proof of principal. Paper presented at 31st Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 13-17, 2018, Dusseldorf, GERMANY. European Journal of Nuclear Medicine and Molecular Imaging, 45, S648-S648
Open this publication in new window or tab >>A novel method for conjugation of PNA to antibodies for radionuclide based pretargeting: proof of principal
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2018 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, p. S648-S648Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
SPRINGER, 2018
National Category
Basic Medicine
Identifiers
urn:nbn:se:kth:diva-239820 (URN)10.1007/s00259-018-4148-3 (DOI)000449266206066 ()2-s2.0-85056052770 (Scopus ID)
Conference
31st Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 13-17, 2018, Dusseldorf, GERMANY
Note

QC 20181217

Available from: 2018-12-18 Created: 2018-12-18 Last updated: 2018-12-18Bibliographically approved
Vorobyeva, A., Westerlund, K., Mitran, B., Altai, M., Rinne, S., Sorensen, J., . . . Tolmachev, V. (2018). Development of a PET Imaging Approach for Selection of Patients for Affibody-Based PNA-Mediated Pretargeted Radionuclide Therapy. Paper presented at 31st Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 13-17, 2018, Dusseldorf, GERMANY. European Journal of Nuclear Medicine and Molecular Imaging, 45, S104-S104
Open this publication in new window or tab >>Development of a PET Imaging Approach for Selection of Patients for Affibody-Based PNA-Mediated Pretargeted Radionuclide Therapy
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2018 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, p. S104-S104Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
SPRINGER, 2018
National Category
Basic Medicine
Identifiers
urn:nbn:se:kth:diva-239825 (URN)10.1007/s00259-018-4148-3 (DOI)000449266201004 ()2-s2.0-85056052770 (Scopus ID)
Conference
31st Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 13-17, 2018, Dusseldorf, GERMANY
Note

QC 20181217

Available from: 2018-12-18 Created: 2018-12-18 Last updated: 2018-12-18Bibliographically approved
Vorobyeva, A., Westerlund, K., Mitran, B., Altai, M., Rinne, S., Sörensen, J., . . . Eriksson Karlström, A. (2018). Development of an optimal imaging strategy for selection of patients for affibody-based PNA-mediated radionuclide therapy. Scientific Reports, 8(1), Article ID 9643.
Open this publication in new window or tab >>Development of an optimal imaging strategy for selection of patients for affibody-based PNA-mediated radionuclide therapy
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2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, no 1, article id 9643Article in journal (Refereed) Published
Abstract [en]

Affibody molecules are engineered scaffold proteins, which demonstrated excellent binding to selected tumor-associated molecular abnormalities in vivo and highly sensitive and specific radionuclide imaging of Her2-expressing tumors in clinics. Recently, we have shown that peptide nucleic acid (PNA)-mediated affibody-based pretargeted radionuclide therapy using beta-emitting radionuclide 177Lu extended significantly survival of mice bearing human Her2-expressing tumor xenografts. In this study, we evaluated two approaches to use positron emission tomography (PET) for stratification of patients for affibody-based pretargeting therapy. The primary targeting probe ZHER2:342-SR-HP1 and the secondary probe HP2 (both conjugated with DOTA chelator) were labeled with the positron-emitting radionuclide 68Ga. Biodistribution of both probes was measured in BALB/C nu/nu mice bearing either SKOV-3 xenografts with high Her2 expression or DU-145 xenografts with low Her2 expression. 68Ga-HP2 was evaluated in the pretargeting setting. Tumor uptake of both probes was compared with the uptake of pretargeted 177Lu-HP2. The uptake of both 68Ga-ZHER2:342-SR-HP1 and 68Ga-HP2 depended on Her2-expression level providing clear discrimination of between tumors with high and low Her2 expression. Tumor uptake of 68Ga-HP2 correlated better with the uptake of 177Lu-HP2 than the uptake of 68Ga-ZHER2:342-SR-HP1. The use of 68Ga-HP2 as a theranostics counterpart would be preferable approach for clinical translation. 

Place, publisher, year, edition, pages
Nature Publishing Group, 2018
National Category
Chemical Sciences
Identifiers
urn:nbn:se:kth:diva-236553 (URN)10.1038/s41598-018-27886-0 (DOI)000436078500006 ()2-s2.0-85049217625 (Scopus ID)
Funder
Swedish Cancer Society, CAN 2015/350 2014/474Swedish Research Council, 2015-02353 2015-02509 2016-05207VINNOVA, 2015-02509Swedish Society for Medical Research (SSMF)
Note

QC 20181127

Available from: 2018-11-27 Created: 2018-11-27 Last updated: 2018-11-27Bibliographically approved
Westerlund, K., Altai, M., Mitran, B., Konijnenberg, M., Oroujeni, M., Atterby, C., . . . Tolmachev, V. (2018). Radionuclide Therapy of HER2-Expressing Human Xenografts Using Affibody-Based Peptide Nucleic Acid-Mediated Pretargeting: In Vivo Proof of Principle. Journal of Nuclear Medicine, 59(7), 1092-1098
Open this publication in new window or tab >>Radionuclide Therapy of HER2-Expressing Human Xenografts Using Affibody-Based Peptide Nucleic Acid-Mediated Pretargeting: In Vivo Proof of Principle
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2018 (English)In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 59, no 7, p. 1092-1098Article in journal (Refereed) Published
Abstract [en]

Affibody molecules are small proteins engineered using a nonanti-body scaffold. Radiolabeled Affibody molecules are excellent imaging probes, but their application to radionuclide therapy has been prevented by high renal reabsorption. The aim of this study was to test the hypothesis that Affibody-based peptide nucleic acid (PNA)-mediated pretargeted therapy of human epidermal growth factor receptor 2 (HER2)-expressing cancer extends survival without accompanying renal toxicity. Methods: A HER2-targeting Affibody molecule ligated with an AGTCGTGATGTAGTC PNA hybridization probe (Z(HER2:342)-SR-HP1) was used as the primary pretargeting agent. A complementary AGTCGTGATGTAGTC PNA conjugated to the chelator DOTA and labeled with the radionuclide Lu-177 (Lu-177-HP2) was used as the secondary agent. The influence of different factors on pretargeting was investigated. Experimental radionuclide therapy in mice bearing SKOV-3 xenografts was performed in 6 cycles separated by 7 d. Results: Optimal tumor targeting was achieved when 16 MBq/3.5 mu g (0.65 nmol) of Lu-177-HP2 was injected 16 h after injection of 100 mu g (7.7 nmol) of Z(HER2:342)-SR-HP1. The calculated absorbed dose to tumors was 1,075 mGy/MBq, whereas the absorbed dose to kidneys was 206 mGy/MBq and the absorbed dose to blood (surrogate of bone marrow) was 4 mGy/MBq. Survival of mice was significantly longer (P < 0.05) in the treatment group (66 d) than in the control groups treated with the same amount of Z(HER2:342)-SR-HP1 only (37 d), the same amount and activity of Lu-177-HP2 only (32 d), or phosphate-buffered saline (37 d). Conclusion: The studied pretargeting system can deliver an absorbed dose to tumors appreciably exceeding absorbed doses to critical organs, making Affibody-based PNA-mediated pretargeted radionuclide therapy highly attractive.

Place, publisher, year, edition, pages
SOC NUCLEAR MEDICINE INC, 2018
Keywords
pretargeting, PNA, affibody molecules, radionuclide therapy, HER2
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:kth:diva-232408 (URN)10.2967/jnumed.118.208348 (DOI)000437237200028 ()29439013 (PubMedID)2-s2.0-85049158654 (Scopus ID)
Note

QC 20180726

Available from: 2018-07-26 Created: 2018-07-26 Last updated: 2018-07-26Bibliographically approved
Horak, J., Jansson, R., Dev, A., Nilebäck, L., Behnam, K., Linnros, J., . . . Eriksson Karlström, A. (2018). Recombinant Spider Silk as Mediator for One-Step, Chemical-Free Surface Biofunctionalization. Advanced Functional Materials, 28(21), Article ID 1800206.
Open this publication in new window or tab >>Recombinant Spider Silk as Mediator for One-Step, Chemical-Free Surface Biofunctionalization
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2018 (English)In: Advanced Functional Materials, ISSN 1616-301X, E-ISSN 1616-3028, Vol. 28, no 21, article id 1800206Article in journal (Refereed) Published
Abstract [en]

A unique strategy for effective, versatile, and facile surface biofunctionalization employing a recombinant spider silk protein genetically functionalized with the antibody-binding Z domain (Z-4RepCT) is reported. It is demonstrated that Z-silk can be applied to a variety of materials and platform designs as a truly one-step and chemical-free surface modification that site specifically captures antibodies while simultaneously reducing nonspecific adsorption. As a model surface, SiO2 is used to optimize and characterize Z-silk performance compared to the Z domain immobilized by a standard silanization method. First, Z-silk adsorption is investigated and verified its biofunctionality in a long-term stability experiment. To assess the binding capacity and protein-protein interaction stability of Z-silk, the coating is used to capture human antibodies in various assay formats. An eightfold higher binding capacity and 40-fold lower detection limit are obtained in the immunofluorescence assay, and the complex stability of captured antibodies is shown to be improved by a factor of 20. Applicability of Z-silk to functionalize microfluidic devices is demonstrated by antibody detection in an electrokinetic microcapillary biosensor. To test Z-silk for biomarker applications, real-time detection and quantification of human immunoglobulin G are performed in a plasma sample and C1q capture from human serum using an anti-C1q antibody.

Place, publisher, year, edition, pages
WILEY-V C H VERLAG GMBH, 2018
Keywords
biomarker, biosensing, C1q, surface biofunctionalization, Z-silk
National Category
Analytical Chemistry
Identifiers
urn:nbn:se:kth:diva-231216 (URN)10.1002/adfm.201800206 (DOI)000434030500011 ()2-s2.0-85047860287 (Scopus ID)
Note

QC 20180628

Available from: 2018-06-28 Created: 2018-06-28 Last updated: 2018-11-23Bibliographically approved
Ståhl, S., Gräslund, T., Eriksson Karlström, A., Frejd, F. Y., Nygren, P.-Å. & Löfblom, J. (2017). Affibody Molecules in Biotechnological and Medical Applications. Trends in Biotechnology, 35(8), 691-712
Open this publication in new window or tab >>Affibody Molecules in Biotechnological and Medical Applications
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2017 (English)In: Trends in Biotechnology, ISSN 0167-7799, E-ISSN 1879-3096, Vol. 35, no 8, p. 691-712Article, review/survey (Refereed) Published
Abstract [en]

Affibody molecules are small (6.5-kDa) affinity proteins based on a three-helix bundle domain framework. Since their introduction 20 years ago as an alternative to antibodies for biotechnological applications, the first therapeutic affibody molecules have now entered clinical development and more than 400 studies have been published in which affibody molecules have been developed and used in a variety of contexts. In this review, we focus primarily on efforts over the past 5 years to explore the potential of affibody molecules for medical applications in oncology, neurodegenerative, and inflammation disorders, including molecular imaging, receptor signal blocking, and delivery of toxic payloads. In addition, we describe recent examples of biotechnological applications, in which affibody molecules have been exploited as modular affinity fusion partners.

Place, publisher, year, edition, pages
Elsevier, 2017
National Category
Biological Sciences
Identifiers
urn:nbn:se:kth:diva-211597 (URN)10.1016/j.tibtech.2017.04.007 (DOI)000405847200005 ()
Note

QC 20170815

Available from: 2017-08-15 Created: 2017-08-15 Last updated: 2017-08-15Bibliographically approved
Tolmachev, V., Yim, C.-B., Rajander, J., Perols, A., Eriksson Karlström, A., Haaparanta-Solin, M., . . . Orlova, A. (2017). Comparative Evaluation of Anti-HER2 Affibody Molecules Labeled with Cu-64 Using NOTA and NODAGA. Contrast Media & Molecular Imaging, 1-12
Open this publication in new window or tab >>Comparative Evaluation of Anti-HER2 Affibody Molecules Labeled with Cu-64 Using NOTA and NODAGA
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2017 (English)In: Contrast Media & Molecular Imaging, ISSN 1555-4309, E-ISSN 1555-4317, p. 1-12Article in journal (Refereed) Published
Abstract [en]

Imaging using affi body molecules enables discrimination between breast cancer metastases with high and low expression of HER2, making appropriate therapy selection possible. This study aimed to evaluate if the longer half-life of Cu-64 (T-1/2 = 12.7h) would make Cu-64 a superior nuclide compared to Ga-68 for PET imaging of HER2 expression using affibody molecules. The synthetic ZHER2: S1 affibody molecule was conjugated with the chelators NOTA or NODAGA and labeled with Cu-64. The tumor-targeting properties of Cu-64-NOTA-ZHER2: S1 and Cu-64-NODAGA-ZHER2: S1 were evaluated and compared with the targeting properties of Ga-68-NODAGA-ZHER2: S1 in mice. Both 64 Cu-NOTA-ZHER2: S1 and Cu-64-NODAGA-ZHER2: S1 demonstrated specific targeting of HER2-expressing xenografts. At 2 h after injection of Cu-64-NOTA-ZHER2: S1, Cu-64-NODAGA-ZHER2: S1, and Ga-68-NODAGAZHER2: S1, tumor uptakes did not differ significantly. Renal uptake of Cu-64-labeled conjugateswas dramatically reduced at 6 and 24 h after injection. Notably, radioactivity uptake concomitantly increased in blood, lung, liver, spleen, and intestines, which resulted in decreased tumor-to-organ ratios compared to 2 h postinjection. Organ uptake was lower for Cu-64-NODAGA-ZHER2: S1. The most probable explanation for this biodistribution pattern was the release and redistribution of renal radiometabolites. In conclusion, monoamide derivatives of NOTA and NODAGA may be suboptimal chelators for radiocopper labeling of anti-HER2 affibody molecules and, possibly, other scaffold proteins with high renal uptake.

Place, publisher, year, edition, pages
WILEY-HINDAWI, 2017
National Category
Biological Sciences
Identifiers
urn:nbn:se:kth:diva-206710 (URN)10.1155/2017/8565802 (DOI)000399198500001 ()2-s2.0-85015751435 (Scopus ID)
Note

QC 20170508

Available from: 2017-05-08 Created: 2017-05-08 Last updated: 2017-05-23Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-0695-5188

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