Reengineering Tumor Microenvironment with Sequential Interleukin Delivery
| Autor: | Rachel A. Letteri, Delphine Chan-Seng, Marxa L. Figueiredo, Todd Emrick, Cosette M. Rivera-Cruz, Shreya Kumar |
|---|---|
| Přispěvatelé: | Purdue University Center for Cancer Research [West Lafayette, IN, USA], Department of Basic Medical Sciences [West Lafayette, IN, USA], Purdue University [West Lafayette], University of Virginia [Charlottesville], Department of Polymer Science and Engineering, University of Massachusetts [Amherst] (UMass Amherst), University of Massachusetts System (UMASS)-University of Massachusetts System (UMASS) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Technology Interleukin-27 QH301-705.5 medicine.medical_treatment Bioengineering Biology Gene delivery Article 03 medical and health sciences Prostate cancer 0302 clinical medicine targeted IL-27pepL medicine sonoporation Interleukin 27 Biology (General) Tumor microenvironment Interleukin-18 Interleukin immune effector signatures medicine.disease prostate cancer 3. Good health sequential delivery 030104 developmental biology Cytokine 030220 oncology & carcinogenesis Cancer cell Cancer research Interleukin 18 [SDV.IB]Life Sciences [q-bio]/Bioengineering |
| Zdroj: | Bioengineering Volume 8 Issue 7 Bioengineering, MDPI, 2021, 8 (7), pp.90. ⟨10.3390/bioengineering8070090⟩ Bioengineering, Vol 8, Iss 90, p 90 (2021) |
| ISSN: | 2306-5354 |
| DOI: | 10.3390/bioengineering8070090 |
| Popis: | International audience; Some cytokines can reengineer anti-tumor immunity to modify the tumor micro-environment. Interleukin-27 (IL-27) can partially reduce tumor growth in several animal models, including prostate cancer. We hypothesized that addition of IL-18, which can induce the proliferation of several immune effector cells through inducing IFNγ could synergize with IL-27 to enhance tumor growth control. We describe our findings on the effects of IL-27 gene delivery on prostate cancer cells and how sequential therapy with IL-18 enhanced the efficacy of IL-27. The combination of IL-27 followed by IL-18 (27→18) successfully reduced cancer cell viability, with significant effects in cell culture and in an immunocompetent mouse model. We also examined a novel chimeric cytokine, comprising an IL-27 targeted at the C-terminus with a short peptide, LSLITRL (27pepL). This novel cytokine targets a receptor upregulated in tumor cells (IL-6Rα) via the pepL ligand. Interestingly, when we compared the 27→18 combination with the single 27pepL therapy, we observed a similar efficacy for both. This efficacy was further enhanced when 27pepL was sequenced with IL-18 (27pepL→18). The observed reduction in tumor growth and significantly enriched canonical pathways and upstream regulators, as well as specific immune effector signatures (as determined by bioinformatics analyses in the tumor microenvironment) supported the therapeutic design, whereby IL-27 or 27pepL can be more effective when delivered with IL-18. This cytokine sequencing approach allows flexible incorporation of both gene delivery and recombinant cytokines as tools to augment IL-27’s bioactivity and reengineer efficacy against prostate tumors and may prove applicable in other therapeutic settings. |
| Databáze: | OpenAIRE |
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