| Title |
Inhibiting IL-2 signaling and the regulatory T-cell pathway using computationally designed peptides
|
|---|---|
| Published in |
Investigational New Drugs, April 2018
|
| DOI | 10.1007/s10637-018-0606-9 |
| Pubmed ID | |
| Authors |
Tammy Price-Troska, Zhi-Zhang Yang, David Diller, Alexander Bayden, Mark Jarosinski, Joseph Audie, Stephen M. Ansell |
| Abstract |
Background Increased serum levels of soluble interleukin-2 (IL-2) receptor alpha (sIL-2Rα) are an indicator of poor prognosis in patients with B-cell non-Hodgkin lymphoma (NHL). By binding to IL-2, sIL-2Rα upregulates Foxp3 expression and induces the development of regulatory T (Treg) cells. Methods To inhibit the binding of IL-2 to sIL-2Rα with the goal of suppressing the induction of Foxp3 and decreasing Treg cell numbers, we developed peptides by structure-based computational design to disrupt the interaction between IL-2 and sIL-2Rα. Each peptide was screened using an enzyme-linked immunosorbent assay (ELISA), and 10 of 22 peptides showed variable capacity to inhibit IL-2/sIL-2Rα binding. Results We identified a lead candidate peptide, CMD178, which consistently reduced the expression of Foxp3 and STAT5 induced by IL-2/sIL-2Rα signaling. Furthermore, production of cytokines (IL-2/interferon gamma [IFN-γ]) and granules (perforin/granzyme B) was preserved in CD8+ T cells co-cultured with IL-2-stimulated CD4+ T cells that had been pretreated with CMD178 compared to CD8+ cells co-cultured with untreated IL-2-stimulated CD4+ T cells where it was inhibited. Conclusions We conclude that structure-based peptide design can be used to identify novel peptide inhibitors that block IL-2/sIL-2Rα signaling and inhibit Treg cell development. We anticipate that these peptides will have therapeutic potential in B-cell NHL and other malignancies. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 14 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 14 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 2 | 14% |
| Student > Doctoral Student | 1 | 7% |
| Student > Bachelor | 1 | 7% |
| Other | 1 | 7% |
| Student > Master | 1 | 7% |
| Other | 3 | 21% |
| Unknown | 5 | 36% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 3 | 21% |
| Neuroscience | 2 | 14% |
| Medicine and Dentistry | 2 | 14% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 7% |
| Physics and Astronomy | 1 | 7% |
| Other | 0 | 0% |
| Unknown | 5 | 36% |
Attention Score in Context
This research output has an Altmetric Attention Score of 13. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 December 2023.
All research outputs
#2,606,693
of 25,090,809 outputs
Outputs from Investigational New Drugs
#58
of 1,254 outputs
Outputs of similar age
#52,496
of 332,424 outputs
Outputs of similar age from Investigational New Drugs
#3
of 18 outputs
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So far Altmetric has tracked 1,254 research outputs from this source. They receive a mean Attention Score of 4.9. This one has done particularly well, scoring higher than 95% of its peers.
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We're also able to compare this research output to 18 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 88% of its contemporaries.