5 Severely immunodeficient NOG-EXL mice allow for humanization and development of a human glioblastoma-derived tumor microenvironment
BackgroundCellular immunotherapy has resulted in tremendous therapeutic advances across liquid tumors. However, for solid tumors, including glioblastoma (GBM), significant limitations still exist in successfully translating immune-based adoptive cell therapeutics from the bench to the clinic. The ma...
Uloženo v:
| Vydáno v: | Journal for immunotherapy of cancer Ročník 11; číslo Suppl 1; s. A5 |
|---|---|
| Hlavní autoři: | , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
London
BMJ Publishing Group Ltd
01.11.2023
BMJ Publishing Group LTD BMJ Publishing Group |
| Témata: | |
| ISSN: | 2051-1426 |
| On-line přístup: | Získat plný text |
| Tagy: |
Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
|
| Abstract | BackgroundCellular immunotherapy has resulted in tremendous therapeutic advances across liquid tumors. However, for solid tumors, including glioblastoma (GBM), significant limitations still exist in successfully translating immune-based adoptive cell therapeutics from the bench to the clinic. The majority of preclinical in vivo GBM models either use human cell lines grown in immunodeficient animals or syngeneic tumors grown in immunocompetent animals. Both approaches lack critical immune components of the tumor microenvironment (TME), thus inherently limiting the ability to adequately model immunotherapies.MethodsHere, we demonstrate the ability of hematopoietic stem cells (HSCs) from a GBM patient to successfully engraft in the severely immunodeficient NOG-EXL mouse strain and generate a patient-derived immune system. Mouse brains, with and without tumors, were evaluated by immunohistochemistry and flow cytometry.ResultsIntraosseous injections of a low number (10,000) of CD34+ HSCs, obtained from a bone marrow draw from the patient at the time of tumor resection, resulted in an average of 20% human CD45+ cells in peripheral blood 17 weeks post-transplant. GBM organoids, established from the same patient, were implanted intracranially at Week 18 and allowed to grow for 5 weeks without significant clinical evidence of graft-vs-host disease or macrophage activation syndrome. Immunohistochemical and flow cytometry analyses of mouse brains, with and without tumors, revealed infiltration of human-derived, CD45+/CD33+ cells, in proximity to the tumor engraftment site.ConclusionsThese results demonstrate the ability of patient-obtained CD34+ HSCs to engraft and form a TME in severely immunodeficient mice. Subsequent work will focus on the differences between autologous and allogeneic humanized tumor-bearing mice in the context of the originating tumor. Additional future work will focus on testing cellular therapies directed towards the relevant areas of the autologous model. |
|---|---|
| AbstractList | BackgroundCellular immunotherapy has resulted in tremendous therapeutic advances across liquid tumors. However, for solid tumors, including glioblastoma (GBM), significant limitations still exist in successfully translating immune-based adoptive cell therapeutics from the bench to the clinic. The majority of preclinical in vivo GBM models either use human cell lines grown in immunodeficient animals or syngeneic tumors grown in immunocompetent animals. Both approaches lack critical immune components of the tumor microenvironment (TME), thus inherently limiting the ability to adequately model immunotherapies.MethodsHere, we demonstrate the ability of hematopoietic stem cells (HSCs) from a GBM patient to successfully engraft in the severely immunodeficient NOG-EXL mouse strain and generate a patient-derived immune system. Mouse brains, with and without tumors, were evaluated by immunohistochemistry and flow cytometry.ResultsIntraosseous injections of a low number (10,000) of CD34+ HSCs, obtained from a bone marrow draw from the patient at the time of tumor resection, resulted in an average of 20% human CD45+ cells in peripheral blood 17 weeks post-transplant. GBM organoids, established from the same patient, were implanted intracranially at Week 18 and allowed to grow for 5 weeks without significant clinical evidence of graft-vs-host disease or macrophage activation syndrome. Immunohistochemical and flow cytometry analyses of mouse brains, with and without tumors, revealed infiltration of human-derived, CD45+/CD33+ cells, in proximity to the tumor engraftment site.ConclusionsThese results demonstrate the ability of patient-obtained CD34+ HSCs to engraft and form a TME in severely immunodeficient mice. Subsequent work will focus on the differences between autologous and allogeneic humanized tumor-bearing mice in the context of the originating tumor. Additional future work will focus on testing cellular therapies directed towards the relevant areas of the autologous model. |
| Author | Radaelli, Enrico Binder, Zev Skuli, Nicholas Lamrani, Lamia Nasrallah, Maclean Jacobson, Moriah Alanio, Cecile Secreto, Anthony O’Rourke, Donald Willis, Elinor Assenmacher, Charles-Antoine |
| Author_xml | – sequence: 1 givenname: Zev surname: Binder fullname: Binder, Zev organization: University of Pennsylvania, Philadelphia, PA, USA – sequence: 2 givenname: Lamia surname: Lamrani fullname: Lamrani, Lamia organization: Institut Curie, Paris, Île-de-France, France – sequence: 3 givenname: Anthony surname: Secreto fullname: Secreto, Anthony organization: University of Pennsylvania, Philadelphia, PA, USA – sequence: 4 givenname: Nicholas surname: Skuli fullname: Skuli, Nicholas organization: University of Pennsylvania, Philadelphia, PA, USA – sequence: 5 givenname: Moriah surname: Jacobson fullname: Jacobson, Moriah organization: Taconic Biosciences, Rockville, MD, USA – sequence: 6 givenname: Charles-Antoine surname: Assenmacher fullname: Assenmacher, Charles-Antoine organization: Comparative Pathology Core, Department of Pathobiology, School of Veterinary Medicine at the University of Pennsylvania, Philadelphia, PA, USA – sequence: 7 givenname: Elinor surname: Willis fullname: Willis, Elinor organization: University of Pennsylvania, Philadelphia, PA, USA – sequence: 8 givenname: Enrico surname: Radaelli fullname: Radaelli, Enrico organization: Comparative Pathology Core, Department of Pathobiology, School of Veterinary Medicine at the University of Pennsylvania, Philadelphia, PA, USA – sequence: 9 givenname: Donald surname: O’Rourke fullname: O’Rourke, Donald organization: University of Pennsylvania, Philadelphia, PA, USA – sequence: 10 givenname: Cecile surname: Alanio fullname: Alanio, Cecile organization: Institut Curie, Paris, Île-de-France, France – sequence: 11 givenname: Maclean surname: Nasrallah fullname: Nasrallah, Maclean organization: University of Pennsylvania, Philadelphia, PA, USA |
| BookMark | eNpFkc-KFDEQh4MouI77DAY895q_3ZmjDOs6MLiHXcFbqHSSNU0nGdPdI-vJi_iePolpR7EuKYpffYT6XqCnKSeH0CtKrijl7ZshzH3DCOPN3f5-tzZXhBD5BF0wImlDBWufo8tpGuqUEs6VUhfop_z1_cedO7nixkccYlxSts6HPrg04w-3N831pwOOoXcYxjF_xT4X_HmJkMI3mENOGJLFtgLGfIzrTvYYzgn8MIZsRpjmHKGxroSTs3heYkVUYskunULJaV17iZ55GCd3-ffdoI_vru9375vD7c1-9_bQGKo62ZieSWFcSyxnilPpaoHYKudbqyRICZ21sgMOpu22vOUgRU-4Vx6YF87zDdqfuTbDoI8lRCiPOkPQfwa5PGgoc-hHpxVvmSTWgLFWAGWVyFsBRjnF-LZecINen1nHkr8sbpr1kJeS6vc1q8cVQtJO1BQ_p0wc_gco0as0vUrTqyv9T5pepfHfYzSStg |
| ContentType | Journal Article |
| Copyright | Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. 2023 Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/ . Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. |
| Copyright_xml | – notice: Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. – notice: 2023 Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/ . Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. |
| DBID | 9YT ACMMV K9. DOA |
| DOI | 10.1136/jitc-2023-SITC2023.0005 |
| DatabaseName | BMJ Open Access Journals (WRLC) BMJ Journals:Open Access ProQuest Health & Medical Complete (Alumni) Open Access: DOAJ - Directory of Open Access Journals |
| DatabaseTitle | ProQuest Health & Medical Complete (Alumni) |
| DatabaseTitleList | ProQuest Health & Medical Complete (Alumni) |
| Database_xml | – sequence: 1 dbid: DOA name: DOAJ Directory of Open Access Journals url: https://www.doaj.org/ sourceTypes: Open Website |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine |
| EISSN | 2051-1426 |
| EndPage | A5 |
| ExternalDocumentID | oai_doaj_org_article_836250dbabdd4a12b67364ab8e823910 jitc |
| GroupedDBID | 4.4 53G 5VS 7X7 88E 8FI 8FJ 9YT ABUWG ACGFS ACMMV ADBBV ADRAZ ADUKV AFKRA AHBYD AHSBF AHYZX ALIPV ALMA_UNASSIGNED_HOLDINGS AMKLP AOIJS ASPBG AVWKF BAWUL BCNDV BENPR BFQNJ BMC BPHCQ BVXVI C6C CCPQU DIK EBS EJD FYUFA GROUPED_DOAJ H13 HMCUK HYE IAO IHR IHW INH INR ITC KQ8 M1P M48 M~E OK1 PHGZT PIMPY PQQKQ PROAC PSQYO RBZ RMJ ROL RPM RSV SOJ UKHRP K9. PHGZM PJZUB PPXIY AFFHD |
| ID | FETCH-LOGICAL-b1875-bc254be60d328315eeeea498ef6d85a55a7dd57a3ab679363a54c03f8fa2f4ef3 |
| IEDL.DBID | DOA |
| IngestDate | Mon Nov 10 04:34:05 EST 2025 Tue Oct 07 06:54:00 EDT 2025 Thu Apr 24 22:49:48 EDT 2025 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | Suppl 1 |
| Language | English |
| License | This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-b1875-bc254be60d328315eeeea498ef6d85a55a7dd57a3ab679363a54c03f8fa2f4ef3 |
| Notes | SITC 38th Annual Meeting (SITC 2023) Abstracts Biomarkers, Immune Monitoring and Novel Technologies ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 |
| OpenAccessLink | https://doaj.org/article/836250dbabdd4a12b67364ab8e823910 |
| PQID | 2888445174 |
| PQPubID | 2040222 |
| ParticipantIDs | doaj_primary_oai_doaj_org_article_836250dbabdd4a12b67364ab8e823910 proquest_journals_2888445174 bmj_journals_10_1136_jitc_2023_SITC2023_0005 |
| PublicationCentury | 2000 |
| PublicationDate | 20231100 20231101 2023-11-01 |
| PublicationDateYYYYMMDD | 2023-11-01 |
| PublicationDate_xml | – month: 11 year: 2023 text: 20231100 |
| PublicationDecade | 2020 |
| PublicationPlace | London |
| PublicationPlace_xml | – name: London |
| PublicationTitle | Journal for immunotherapy of cancer |
| PublicationTitleAbbrev | J Immunother Cancer |
| PublicationYear | 2023 |
| Publisher | BMJ Publishing Group Ltd BMJ Publishing Group LTD BMJ Publishing Group |
| Publisher_xml | – name: BMJ Publishing Group Ltd – name: BMJ Publishing Group LTD – name: BMJ Publishing Group |
| SSID | ssj0001033888 |
| Score | 2.2362509 |
| Snippet | BackgroundCellular immunotherapy has resulted in tremendous therapeutic advances across liquid tumors. However, for solid tumors, including glioblastoma (GBM),... |
| SourceID | doaj proquest bmj |
| SourceType | Open Website Aggregation Database Publisher |
| StartPage | A5 |
| SubjectTerms | Brain cancer Flow cytometry Immunotherapy Regular and Young Investigator Award Abstracts Tumors |
| Title | 5 Severely immunodeficient NOG-EXL mice allow for humanization and development of a human glioblastoma-derived tumor microenvironment |
| URI | https://jitc.bmj.com/content/11/Suppl_1/A5.full https://www.proquest.com/docview/2888445174 https://doaj.org/article/836250dbabdd4a12b67364ab8e823910 |
| Volume | 11 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| journalDatabaseRights | – providerCode: PRVADU databaseName: BioMedCentral databaseCode: RBZ dateStart: 20130101 customDbUrl: isFulltext: true eissn: 2051-1426 dateEnd: 99991231 titleUrlDefault: https://www.biomedcentral.com/search/ omitProxy: false ssIdentifier: ssj0001033888 providerName: BioMedCentral – providerCode: PRVAON databaseName: DOAJ Directory of Open Access Journals databaseCode: DOA dateStart: 20130101 customDbUrl: isFulltext: true eissn: 2051-1426 dateEnd: 99991231 titleUrlDefault: https://www.doaj.org/ omitProxy: false ssIdentifier: ssj0001033888 providerName: Directory of Open Access Journals – providerCode: PRVHPJ databaseName: ROAD: Directory of Open Access Scholarly Resources databaseCode: M~E dateStart: 20130101 customDbUrl: isFulltext: true eissn: 2051-1426 dateEnd: 99991231 titleUrlDefault: https://road.issn.org omitProxy: false ssIdentifier: ssj0001033888 providerName: ISSN International Centre – providerCode: PRVPQU databaseName: Health & Medical Collection databaseCode: 7X7 dateStart: 20130501 customDbUrl: isFulltext: true eissn: 2051-1426 dateEnd: 99991231 titleUrlDefault: https://search.proquest.com/healthcomplete omitProxy: false ssIdentifier: ssj0001033888 providerName: ProQuest – providerCode: PRVPQU databaseName: ProQuest Central databaseCode: BENPR dateStart: 20130501 customDbUrl: isFulltext: true eissn: 2051-1426 dateEnd: 99991231 titleUrlDefault: https://www.proquest.com/central omitProxy: false ssIdentifier: ssj0001033888 providerName: ProQuest – providerCode: PRVPQU databaseName: Publicly Available Content Database databaseCode: PIMPY dateStart: 20130501 customDbUrl: isFulltext: true eissn: 2051-1426 dateEnd: 99991231 titleUrlDefault: http://search.proquest.com/publiccontent omitProxy: false ssIdentifier: ssj0001033888 providerName: ProQuest |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1NT9wwELVaqKpeqlKoSgsrHzjWIont2DkCWihS2a74kLYnaxw7aBG7qSCAuHGp-j_7SzqTBLESh16aUxJZdjR-9szEM28Y28pSIBZvEBHVi1AxqwRkOa4rgAJ9XGmi7YpNmNHITibFeKHUF8WEdfTAneC2Le6wOgkefAgK0sxTIJICb7FzWXTJVYkpFpyp9u9Kgq6XtX1AVyrz7YtpUwqqFS5ODk_36IaoC0ml-NlFT9j_bD9ulcz-O_a2tw75TvdVK-xFnL9nr4_68-9V9lv_efh1EhF-8fKeTym3ow6RSCBQd_DR9wMxnHzjVGGe04H6HUeTlLdl-Pp0Sw7zwMNToBCvKw5dC35-Oa09GtNNPQMREJm3MfDmZoZdzChsbyEnbo2d7Q9P976KvpSC8Cl6JMKX6Aj6mCdBoj2R6ogXqMLGKg9Wg9ZgQtAGJKB8C5lL0KpMZGUryCoVK_mBLc3refzIuJLGo0-IllmsVIrdAJQBMjQbvMbtQa-zLyhR1y-Fa9d6GTJ3NAGO5O4eJ4AOvrH5Lone_ezINRzRXbcvEASuB4H7FwjW2cbjxD0NnCEAiH7NqE__Y4zP7E0LnzYPcYMtNVc3cZO9Km-b6fXVgL00EzNgy7vD0fh40IIRn8aHR-MffwF8OOP1 |
| linkProvider | Directory of Open Access Journals |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=5%E2%80%85Severely+immunodeficient+NOG-EXL+mice+allow+for+humanization+and+development+of+a+human+glioblastoma-derived+tumor+microenvironment&rft.jtitle=Journal+for+immunotherapy+of+cancer&rft.au=Binder%2C+Zev&rft.au=Lamrani%2C+Lamia&rft.au=Secreto%2C+Anthony&rft.au=Skuli%2C+Nicholas&rft.date=2023-11-01&rft.pub=BMJ+Publishing+Group+LTD&rft.eissn=2051-1426&rft.volume=11&rft.issue=Suppl+1&rft.spage=A5&rft.epage=A5&rft_id=info:doi/10.1136%2Fjitc-2023-SITC2023.0005&rft.externalDBID=HAS_PDF_LINK |