دورية أكاديمية
أعرض في EDS

Targeted delivery of CD40L promotes restricted activation of antigen-presenting cells and induction of cancer cell death.

التفاصيل البيبلوغرافية
العنوان: Targeted delivery of CD40L promotes restricted activation of antigen-presenting cells and induction of cancer cell death.
المؤلفون: Brunekreeft KL, Strohm C, Gooden MJ, Rybczynska AA, Nijman HW, Grigoleit GU, Helfrich W, Bremer E, Siegmund D, Wajant H, de Bruyn M; Department of Obstetrics and Gynecology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. m.de.bruyn@umcg.nl.
المصدر: Molecular cancer [Mol Cancer] 2014 Apr 17; Vol. 13, pp. 85. Date of Electronic Publication: 2014 Apr 17.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101147698 Publication Model: Electronic Cited Medium: Internet ISSN: 1476-4598 (Electronic) Linking ISSN: 14764598 NLM ISO Abbreviation: Mol Cancer Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : BioMed Central, c2002-
مواضيع طبية MeSH: B-Lymphocytes/*drug effects , CD40 Ligand/*genetics , Dendritic Cells/*drug effects , Recombinant Fusion Proteins/*pharmacology , Single-Chain Antibodies/*genetics, Antibodies, Monoclonal, Murine-Derived/pharmacology ; Antigens, CD20/genetics ; Antigens, CD20/metabolism ; Antigens, Neoplasm/genetics ; Antigens, Neoplasm/metabolism ; Antineoplastic Agents/pharmacology ; B-Lymphocytes/metabolism ; B-Lymphocytes/pathology ; CD40 Ligand/metabolism ; Cell Adhesion Molecules/genetics ; Cell Adhesion Molecules/metabolism ; Cell Death/drug effects ; Cell Line, Tumor ; Cell Survival/drug effects ; Dendritic Cells/metabolism ; Dendritic Cells/pathology ; Epithelial Cell Adhesion Molecule ; Gene Expression ; HEK293 Cells ; Humans ; Molecular Targeted Therapy ; Recombinant Fusion Proteins/genetics ; Recombinant Fusion Proteins/metabolism ; Rituximab ; Single-Chain Antibodies/metabolism
مستخلص: Background: Stimulation of CD40 can augment anti-cancer T cell immune responses by triggering effective activation and maturation of antigen-presenting cells (APCs). Although CD40 agonists have clinical activity in humans, the associated systemic activation of the immune system triggers dose-limiting side-effects.
Methods: To increase the tumor selectivity of CD40 agonist-based therapies, we developed an approach in which soluble trimeric CD40L (sCD40L) is genetically fused to tumor targeting antibody fragments, yielding scFv:CD40L fusion proteins. We hypothesized that scFv:CD40L fusion proteins would have reduced CD40 agonist activity similar to sCD40L but will be converted to a highly agonistic membrane CD40L-like form of CD40L upon anchoring to cell surface exposed antigen via the scFv domain.
Results: Targeted delivery of CD40L to the carcinoma marker EpCAM on carcinoma cells induced dose-dependent paracrine maturation of DCs ~20-fold more effective than a non-targeted control scFv:CD40L fusion protein. Similarly, targeted delivery of CD40L to the B cell leukemia marker CD20 induced effective paracrine maturation of DCs. Of note, the CD20-selective delivery of CD40L also triggered loss of cell viability in certain B cell leukemic cell lines as a result of CD20-induced apoptosis.
Conclusions: Targeted delivery of CD40L to cancer cells is a promising strategy that may help to trigger cancer-localized activation of CD40 and can be modified to exert additional anti-cancer activity via the targeting domain.
References: Curr Opin Immunol. 1997 Jun;9(3):330-7. (PMID: 9203418)
J Immunol. 2009 Aug 1;183(3):1851-61. (PMID: 19596991)
Cancer Res. 2008 Jan 15;68(2):597-604. (PMID: 18199557)
Expert Opin Biol Ther. 2013 May;13(5):803-11. (PMID: 23560506)
Nature. 1998 Jun 4;393(6684):474-8. (PMID: 9624003)
Int Rev Immunol. 2012 Aug;31(4):246-66. (PMID: 22804570)
Clin Cancer Res. 2011 Sep 1;17(17):5626-37. (PMID: 21753155)
Scand J Immunol. 2007 Nov;66(5):501-7. (PMID: 17953526)
Clin Cancer Res. 2003 Apr;9(4):1517-27. (PMID: 12684428)
Vaccine. 2008 Jul 29;26(32):4006-14. (PMID: 18562050)
FEBS Lett. 1993 Jan 11;315(3):259-66. (PMID: 7678552)
J Immunol. 2000 Dec 1;165(11):6047-55. (PMID: 11086036)
Scand J Immunol. 2007 May;65(5):479-86. (PMID: 17444959)
Science. 2011 Mar 25;331(6024):1612-6. (PMID: 21436454)
Immunity. 2008 Sep 19;29(3):372-83. (PMID: 18799145)
Eur J Immunol. 2001 Oct;31(10):3094-100. (PMID: 11592086)
Oncoimmunology. 2013 Jan 1;2(1):e23033. (PMID: 23483678)
Clin Cancer Res. 2011 Apr 15;17(8):2270-80. (PMID: 21389097)
Cancer Biol Ther. 2010 Nov 15;10(10):983-93. (PMID: 20855968)
ISRN Oncol. 2013 Jun 11;2013:371854. (PMID: 23840967)
J Immunol. 2011 Aug 15;187(4):1754-63. (PMID: 21742972)
J Hematother. 1995 Oct;4(5):409-14. (PMID: 8581377)
J Clin Oncol. 2001 Jul 1;19(13):3280-7. (PMID: 11432896)
Oncoimmunology. 2013 Jan 1;2(1):e22546. (PMID: 23483661)
J Immunol. 2007 Jul 15;179(2):1362-8. (PMID: 17617629)
Blood. 2012 Oct 11;120(15):3030-8. (PMID: 22932804)
J Clin Oncol. 2007 Mar 1;25(7):876-83. (PMID: 17327609)
Int J Cancer. 2013 May 1;132(9):1971-6. (PMID: 22858832)
Nat Cell Biol. 2009 Feb;11(2):162-71. (PMID: 19136966)
Circ Res. 2003 May 16;92(9):944-6. (PMID: 12750303)
Cancer Lett. 2013 May 28;332(2):175-83. (PMID: 21215513)
Nat Med. 1999 May;5(5):548-53. (PMID: 10229232)
Curr Drug Targets. 2009 Feb;10(2):94-103. (PMID: 19199904)
J Mol Med (Berl). 1999 Oct;77(10):699-712. (PMID: 10606205)
Expert Opin Biol Ther. 2013 Feb;13(2):169-82. (PMID: 23256681)
المشرفين على المادة: 0 (Antibodies, Monoclonal, Murine-Derived)
0 (Antigens, CD20)
0 (Antigens, Neoplasm)
0 (Antineoplastic Agents)
0 (Cell Adhesion Molecules)
0 (EPCAM protein, human)
0 (Epithelial Cell Adhesion Molecule)
0 (Recombinant Fusion Proteins)
0 (Single-Chain Antibodies)
147205-72-9 (CD40 Ligand)
4F4X42SYQ6 (Rituximab)
تواريخ الأحداث: Date Created: 20140419 Date Completed: 20150112 Latest Revision: 20211021
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC4022212
DOI: 10.1186/1476-4598-13-85
PMID: 24741998
قاعدة البيانات: MEDLINE
الوصف
تدمد:1476-4598
DOI:10.1186/1476-4598-13-85