دورية أكاديمية
أعرض في EDS

Novel combination immunotherapy for pancreatic cancer: potent anti-tumor effects with CD40 agonist and interleukin-15 treatment.

التفاصيل البيبلوغرافية
العنوان: Novel combination immunotherapy for pancreatic cancer: potent anti-tumor effects with CD40 agonist and interleukin-15 treatment.
المؤلفون: Van Audenaerde JR; Center for Oncological Research (CORE) Integrated Personalized & Precision Oncology Network (IPPON) University of Antwerp Wilrijk Belgium.; Cancer Immunotherapy and Immune Innovation Laboratory Peter MacCallum Cancer Centre Melbourne VIC Australia., Marcq E; Center for Oncological Research (CORE) Integrated Personalized & Precision Oncology Network (IPPON) University of Antwerp Wilrijk Belgium., von Scheidt B; Cancer Immunotherapy and Immune Innovation Laboratory Peter MacCallum Cancer Centre Melbourne VIC Australia., Davey AS; Cancer Immunotherapy and Immune Innovation Laboratory Peter MacCallum Cancer Centre Melbourne VIC Australia., Oliver AJ; Cancer Immunotherapy and Immune Innovation Laboratory Peter MacCallum Cancer Centre Melbourne VIC Australia., De Waele J; Center for Oncological Research (CORE) Integrated Personalized & Precision Oncology Network (IPPON) University of Antwerp Wilrijk Belgium., Quatannens D; Center for Oncological Research (CORE) Integrated Personalized & Precision Oncology Network (IPPON) University of Antwerp Wilrijk Belgium., Van Loenhout J; Center for Oncological Research (CORE) Integrated Personalized & Precision Oncology Network (IPPON) University of Antwerp Wilrijk Belgium., Pauwels P; Center for Oncological Research (CORE) Integrated Personalized & Precision Oncology Network (IPPON) University of Antwerp Wilrijk Belgium.; Department of Pathology Antwerp University Hospital Edegem Belgium., Roeyen G; Department of Hepatobiliary, Endocrine and Transplantation Surgery Antwerp University Hospital Edegem Belgium., Lardon F; Center for Oncological Research (CORE) Integrated Personalized & Precision Oncology Network (IPPON) University of Antwerp Wilrijk Belgium., Slaney CY; Cancer Immunotherapy and Immune Innovation Laboratory Peter MacCallum Cancer Centre Melbourne VIC Australia.; Sir Peter MacCallum Department of Oncology The University of Melbourne Parkville VIC Australia., Peeters M; Center for Oncological Research (CORE) Integrated Personalized & Precision Oncology Network (IPPON) University of Antwerp Wilrijk Belgium.; Department of Oncology and Multidisciplinary Oncological Centre Antwerp Antwerp University Hospital Edegem Belgium., Kershaw MH; Cancer Immunotherapy and Immune Innovation Laboratory Peter MacCallum Cancer Centre Melbourne VIC Australia.; Sir Peter MacCallum Department of Oncology The University of Melbourne Parkville VIC Australia., Darcy PK; Cancer Immunotherapy and Immune Innovation Laboratory Peter MacCallum Cancer Centre Melbourne VIC Australia.; Sir Peter MacCallum Department of Oncology The University of Melbourne Parkville VIC Australia., Smits EL; Center for Oncological Research (CORE) Integrated Personalized & Precision Oncology Network (IPPON) University of Antwerp Wilrijk Belgium.; Center for Cell Therapy and Regenerative Medicine Antwerp University Hospital Edegem Belgium.
المصدر: Clinical & translational immunology [Clin Transl Immunology] 2020 Aug 15; Vol. 9 (8), pp. e1165. Date of Electronic Publication: 2020 Aug 15 (Print Publication: 2020).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: John Wiley & Sons Australia, Ltd. on behalf of Australasian Society for Immunology Inc Country of Publication: Australia NLM ID: 101638268 Publication Model: eCollection Cited Medium: Print ISSN: 2050-0068 (Print) Linking ISSN: 20500068 NLM ISO Abbreviation: Clin Transl Immunology Subsets: PubMed not MEDLINE
أسماء مطبوعة: Publication: 2018- : [Milton, Queensland] : John Wiley & Sons Australia, Ltd. on behalf of Australasian Society for Immunology Inc.
Original Publication: [London] : Nature Publishing Group, 2012-
مستخلص: Objectives: With the poorest 5-year survival of all cancers, improving treatment for pancreatic cancer is one of the biggest challenges in cancer research. We sought to explore the potential of combining both priming and activation of the immune system. To achieve this, we combined a CD40 agonist with interleukin-15 and tested its potential in pancreatic cancer.
Methods: Response to this combination regimen was assessed in pancreatic ductal adenocarcinoma mouse models, and a thorough analysis of the tumor microenvironment was performed.
Results: We demonstrated profound reduction in tumor growth and increased survival of mice with the majority of mice being cured when both agents were combined, including an unprecedented 8-fold dose reduction of CD40 agonist without losing any efficacy. RNAseq analysis showed involvement of natural killer (NK) cell- and T-cell-mediated anti-tumor responses and the importance of antigen-presenting cell pathways. This combination resulted in enhanced infiltration of tumors by both T cells and NK cells, as well as a striking increase in the ratio of CD8 + T cells over Tregs. We also observed a significant increase in numbers of dendritic cells (DCs) in tumor-draining lymph nodes, particularly CD103 + DCs with cross-presentation potential. A critical role for CD8 + T cells and involvement of NK cells in the anti-tumor effect was highlighted. Importantly, strong immune memory was established, with an increase in memory CD8 + T cells only when both interleukin-15 and the CD40 agonist were combined.
Conclusion: These novel preclinical data support initiation of a first-in-human clinical trial with this combination immunotherapy strategy in pancreatic cancer.
Competing Interests: The authors declare no conflict of interest.
(© 2020 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)
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فهرسة مساهمة: Keywords: CD40 agonist; T cells; combination immunotherapy; interleukin‐15; natural killer cells; pancreatic cancer
تواريخ الأحداث: Date Created: 20200822 Latest Revision: 20220416
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC7428816
DOI: 10.1002/cti2.1165
PMID: 32821382
قاعدة البيانات: MEDLINE
الوصف
تدمد:2050-0068
DOI:10.1002/cti2.1165