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WFRF:(Lilja Hans G.)
 

Sökning: WFRF:(Lilja Hans G.) > Genetic signature o...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00006195naa a2200637 4500
001oai:lup.lub.lu.se:d9e979bd-51e7-42c2-8c18-ab3712b435e6
003SwePub
008200716s2020 | |||||||||||000 ||eng|
0247 a https://lup.lub.lu.se/record/d9e979bd-51e7-42c2-8c18-ab3712b435e62 URI
0247 a https://doi.org/10.1073/pnas.19187441172 DOI
040 a (SwePub)lu
041 a engb eng
042 9 SwePub
072 7a art2 swepub-publicationtype
072 7a ref2 swepub-contenttype
1001 a Bicak, Mesudeu Icahn School of Medicine at Mount Sinai4 aut
2451 0a Genetic signature of prostate cancer mouse models resistant to optimized hK2 targeted α-particle therapy
264 c 2020-06-12
264 1b Proceedings of the National Academy of Sciences,c 2020
300 a 10 s.
520 a Hu11B6 is a monoclonal antibody that internalizes in cells expressing androgen receptor (AR)-regulated prostate-specific enzyme human kallikrein-related peptidase 2 (hK2; KLK2). In multiple rodent models, Actinium-225-labeled hu11B6-IgG1 ([225Ac]hu11B6-IgG1) has shown promising treatment efficacy. In the present study, we investigated options to enhance and optimize [225Ac]hu11B6 treatment. First, we evaluated the possibility of exploiting IgG3, the IgG subclass with superior activation of complement and ability to mediate FC-γ-receptor binding, for immunotherapeutically enhanced hK2 targeted α-radioimmunotherapy. Second, we compared the therapeutic efficacy of a single high activity vs. fractionated activity. Finally, we used RNA sequencing to analyze the genomic signatures of prostate cancer that progressed after targeted α-therapy. [225Ac]hu11B6-IgG3 was a functionally enhanced alternative to [225Ac]hu11B6-IgG1 but offered no improvement of therapeutic efficacy. Progression-free survival was slightly increased with a single high activity compared to fractionated activity. Tumor-free animals succumbing after treatment revealed no evidence of treatment-associated toxicity. In addition to up-regulation of canonical aggressive prostate cancer genes, such as MMP7, ETV1, NTS, and SCHLAP1, we also noted a significant decrease in both KLK3 (prostate-specific antigen ) and FOLH1 (prostate-specific membrane antigen) but not in AR and KLK2, demonstrating efficacy of sequential [225Ac]hu11B6 in a mouse model.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Medicinsk genetik0 (SwePub)301072 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Medical Genetics0 (SwePub)301072 hsv//eng
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Cancer och onkologi0 (SwePub)302032 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cancer and Oncology0 (SwePub)302032 hsv//eng
650 7a NATURVETENSKAPx Fysikx Annan fysik0 (SwePub)103992 hsv//swe
650 7a NATURAL SCIENCESx Physical Sciencesx Other Physics Topics0 (SwePub)103992 hsv//eng
653 a 225Ac
653 a hK2
653 a hu11B6
653 a prostate cancer
653 a radiommunotherapy
7001 a Lückerath, Katharinau University of California, Los Angeles4 aut
7001 a Kalidindi, Tejau Memorial Sloan-Kettering Cancer Center4 aut
7001 a Phelps, Michael E.u University of California, Los Angeles4 aut
7001 a Strand, Sven Eriku Lund University,Lunds universitet,Medicinsk strålningsfysik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Forskningsgruppen för Systemisk strålterapi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Strålterapi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medical Radiation Physics, Lund,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Systemic Radiation Therapy Group,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Radiation therapy,Section I,Department of Clinical Sciences, Lund4 aut0 (Swepub:lu)rafy-ses
7001 a Morris, Michael J.u Memorial Sloan-Kettering Cancer Center4 aut
7001 a Radu, Caius G.u University of California, Los Angeles4 aut
7001 a Damoiseaux, Robertu University of California, Los Angeles4 aut
7001 a Peltola, Mari T.u University of Turku4 aut
7001 a Peekhaus, Norbertu University of California, Los Angeles4 aut
7001 a Ho, Austinu University of California, Los Angeles4 aut
7001 a Veach, Darrenu Diaprost AB,Memorial Sloan-Kettering Cancer Center4 aut
7001 a Malmborg Hager, Ann Christinu Diaprost AB4 aut0 (Swepub:lu)immt-acm
7001 a Larson, Steven M.u Memorial Sloan-Kettering Cancer Center,Cornell University4 aut
7001 a Lilja, Hansu Lund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Clinical Chemistry, Malmö,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Memorial Sloan-Kettering Cancer Center,University of Oxford4 aut0 (Swepub:lu)klke-hli
7001 a McDevitt, Michael R.u Memorial Sloan-Kettering Cancer Center4 aut
7001 a Klein, Robert J.u Icahn School of Medicine at Mount Sinai4 aut
7001 a Ulmert, Davidu University of California, Los Angeles4 aut0 (Swepub:lu)klke-dul
7102 a Icahn School of Medicine at Mount Sinaib University of California, Los Angeles4 org
7730 t Proceedings of the National Academy of Sciences of the United States of Americad : Proceedings of the National Academy of Sciencesg 117:26, s. 15172-15181q 117:26<15172-15181x 1091-6490
7730 t Proceedings of the National Academy of Sciencesd : Proceedings of the National Academy of Sciencesg 117:26, s. 15172-15181q 117:26<15172-15181x 0027-8424
8564 u http://dx.doi.org/10.1073/pnas.1918744117y FULLTEXT
8564 u https://www.pnas.org/content/pnas/117/26/15172.full.pdf
8564 8u https://lup.lub.lu.se/record/d9e979bd-51e7-42c2-8c18-ab3712b435e6
8564 8u https://doi.org/10.1073/pnas.1918744117

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