ArticleClinical & translational immunology2020
Novel combination immunotherapy for pancreatic cancer: potent anti-tumor effects with CD40 agonist and interleukin-15 treatment.
Article in Clinical & translational immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- IL-15 complex enhances therapeutic efficacy of anti-PD-L1 in a T cell-dependent and NK cell-independent manner in a murine model of pancreatic ductal adenocarcinoma.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Development of a peptide-based tumor-activated checkpoint inhibitor for cancer immunotherapy.Acta biomaterialia · 2025Article
- Based on the immune system: the role of the IL-2 family in pancreatic disease.Frontiers in immunology · 2025Review
- Type I conventional dendritic cells facilitate immunotherapy in pancreatic cancer.Science (New York, N.Y.) · 2024Article
- Bridging Chronic Inflammation and Digestive Cancer: The Critical Role of Innate Lymphoid Cells in Tumor Microenvironments.International journal of biological sciences · 2024Review
- Natural killer cells for pancreatic cancer immunotherapy: Role of nanoparticles.Cancer letters · 2023Article
- IL-15 synergizes with CD40 agonist antibodies to induce durable immunity against bladder cancer.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Immunotherapy for Prostate Cancer: A Current Systematic Review and Patient Centric Perspectives.Journal of clinical medicine · 2023Article
- IL-15 synergizes with CD40 agonist antibodies to induce durable immunity against bladder cancer.bioRxiv : the preprint server for biology · 2023Article
- Targeting CD70 in combination with chemotherapy to enhance the anti-tumor immune effects in non-small cell lung cancer.Oncoimmunology · 2023Article
- The effect of local non-thermal plasma therapy on the cancer-immunity cycle in a melanoma mouse model.Bioengineering & translational medicine · 2022Article
- The Trinity: Interplay among Cancer Cells, Fibroblasts, and Immune Cells in Pancreatic Cancer and Implication of CD8Biomedicines · 2022Review
- Application of natural killer cells in pancreatic cancer.Oncology letters · 2021Review
- Review
- Chronic inflammation promotes epithelial-mesenchymal transition-mediated malignant phenotypes and lung injury in experimentally-induced pancreatitis.Life sciences · 2021Article
- Therapeutic potential of interleukin-15 in cancer (Review).Experimental and therapeutic medicine · 2021Review
- Natural killer cells in pancreatic cancer stroma.World journal of gastroenterology · 2021Review
- The State-of-the-Art of Phase II/III Clinical Trials for Targeted Pancreatic Cancer Therapies.Journal of clinical medicine · 2021Review
- The Search for an Interesting Partner to Combine with PD-L1 Blockade in Mesothelioma: Focus on TIM-3 and LAG-3.Cancers · 2021Article
- Enhancing co-stimulation of CAR T cells to improve treatment outcomes in solid cancers.Immunotherapy advances · 2021Review
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesWith 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.
methodsResponse to this combination regimen was assessed in pancreatic ductal adenocarcinoma mouse models, and a thorough analysis of the tumor microenvironment was performed.
resultsWe 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
conclusionThese novel preclinical data support initiation of a first-in-human clinical trial with this combination immunotherapy strategy in pancreatic cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.