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Melittin-MIL-2 fusion protein as a candidate for cancer immunotherapy

Overview of attention for article published in Journal of Translational Medicine, June 2016
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  • Good Attention Score compared to outputs of the same age and source (70th percentile)

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Title
Melittin-MIL-2 fusion protein as a candidate for cancer immunotherapy
Published in
Journal of Translational Medicine, June 2016
DOI 10.1186/s12967-016-0910-0
Pubmed ID
Authors

Mingjun Liu, Haitao Wang, Linjie Liu, Bin Wang, Guirong Sun

Abstract

Cytokine fusion protein that modulates the immune response holds great potential for cancer immunotherapy. IL-2 is an effective treatment against advanced cancers. However, the therapeutic efficacy of IL-2 is limited by severe systemic toxicity. Several mutants recombinant IL-2 can increase antitumor activity and minimize systemic toxicity. Melittin is an attractive anticancer candidate because of its wide-spectrum lytic properties. We previously generated a bifunctional fusion protein melittin-MIL-2, composed of melittin and a mutant IL-2. The melittin-MIL-2 inhibited the growth of human ovarian cancer SKOV3 cells in vitro and in vivo tumor growth. However, whether this antitumor effect could also be used in cancer immunotherapy was unknown. To assess its cancer immunotherapy potential, we further investigated its more effective antitumor immune response and antitumor effect against cancers of different tissue origins in vitro and in vivo. The specific IL-2 activity of the melittin-MIL-2 fusion protein was tested on the cytokine growth dependent cell line CTLL-2. The cytolytic activity was detected by standard 4-h (51)Cr-release assays. PBMC stimulation in response to the melittin-MIL-2 was determined by IFN-γ release assay. We observed the cancer cell proliferation of different tissue origins by MTT assay. The ability of melittin-MIL-2 to inhibit tumor growth in vivo was evaluated by using human liver (SMMC-7721 cancer cells), lung (A549 cancer cells) and ovarian (SKOV3 cancer cells) cancer xenograft models. To assess the immunity within the tumor microenvironment, the level of some cytokines including IFN-γ, TNF-α, IL-12 and IL-4 was analyzed by ELISA. We injected the MDA-MB-231 cells and the melittin-MIL-2 into mice, and the anti-metastatic effect was examined by counting nodules in the lung. The melittin-MIL-2 was more effective in inducing T cell and NK-cell cytotoxicity. The fusion protein significantly increased IFN-γ production in PBMCs. In vitro, the melittin-MIL-2 mediated immune cells killing or directly killed the cancer cell lines of different tissue origins. In vivo, the fusion protein exhibited stronger inhibition on the growth of transplanted human tumors compared to rIL-2. The melittin-MIL-2 treatment promoted the IFN-γ secretion in tumor tissues and decreased the immunosuppressive cells in vivo. Furthermore, the fusion protein reduced lung metastasis of breast cancer. This study provides the evidence that the melittin-MIL-2 can produce stronger immune stimulation and antitumor effects, and the fusion protein is a potent candidate for cancer immunotherapy.

X Demographics

X Demographics

The data shown below were collected from the profiles of 7 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 52 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
India 1 2%
Sweden 1 2%
Unknown 50 96%

Demographic breakdown

Readers by professional status Count As %
Student > Master 8 15%
Researcher 6 12%
Student > Ph. D. Student 6 12%
Student > Bachelor 4 8%
Student > Doctoral Student 3 6%
Other 7 13%
Unknown 18 35%
Readers by discipline Count As %
Medicine and Dentistry 8 15%
Biochemistry, Genetics and Molecular Biology 7 13%
Pharmacology, Toxicology and Pharmaceutical Science 6 12%
Immunology and Microbiology 3 6%
Agricultural and Biological Sciences 3 6%
Other 5 10%
Unknown 20 38%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 4. 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 22 April 2020.
All research outputs
#7,261,572
of 23,109,468 outputs
Outputs from Journal of Translational Medicine
#1,168
of 4,060 outputs
Outputs of similar age
#115,650
of 339,972 outputs
Outputs of similar age from Journal of Translational Medicine
#34
of 114 outputs
Altmetric has tracked 23,109,468 research outputs across all sources so far. This one has received more attention than most of these and is in the 68th percentile.
So far Altmetric has tracked 4,060 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.6. This one has gotten more attention than average, scoring higher than 71% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 339,972 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 65% of its contemporaries.
We're also able to compare this research output to 114 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 70% of its contemporaries.