Evidence map›Paper›PMID 28574833›Full record

ArticleOncotarget2017

New interleukin-15 superagonist (IL-15SA) significantly enhances graft-versus-tumor activity.

Cavan P Bailey, Tulin Budak-Alpdogan, Christopher T Sauter, Michelle M Panis, Cihangir Buyukgoz, Emily K Jeng, Hing C Wong, Neal Flomenberg, Onder Alpdogan

Abstract read
In one paragraph

Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. T cell regeneration after immunological injury.Nature reviews. Immunology · 2021
    Review
  9. Review
  10. Review
  11. Article
  12. Engineering Platforms for T Cell Modulation.International review of cell and molecular biology · 2018
    Review
  13. Review
  14. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Cavan P BaileyDepartment of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
Tulin Budak-AlpdoganDepartment of Hematology and Oncology, MD Anderson Cancer Center at Cooper, Camden, NJ, USA.
Christopher T SauterDepartment of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
Michelle M PanisDepartment of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
Cihangir BuyukgozDepartment of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
Emily K JengAltor BioScience Corporation, Miramar, FL, USA.
Hing C WongAltor BioScience Corporation, Miramar, FL, USA.
Neal FlomenbergDepartment of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
Onder AlpdoganDepartment of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Interleukin-15 (IL-15) is a potent cytokine that increases CD8+ T and NK cell numbers and function in experimental models. However, obstacles remain in using IL-15 therapeutically, specifically its low potency and short in vivo half-life. To help overcome this, a new IL-15 superagonist complex comprised of an IL-15N72D mutation and IL-15RαSu/Fc fusion (IL-15SA, also known as ALT-803) was developed. IL-15SA exhibits a significantly longer serum half-life and increased in vivo activity against various tumors. Herein, we evaluated the effects of IL-15SA in recipients of allogeneic hematopoietic stem cell transplantation. Weekly administration of IL-15SA to transplant recipients significantly increased the number of CD8+ T cells (specifically CD44+ memory/activated phenotype) and NK cells. Intracellular IFN-γ and TNF-α secretion by CD8+ T cells increased in the IL-15SA-treated group. IL-15SA also upregulated NKG2D expression on CD8+ T cells. Moreover, IL-15SA enhanced proliferation and cytokine secretion of adoptively transferred CFSE-labeled T cells in syngeneic and allogeneic models by specifically stimulating the slowly proliferative and nonproliferative cells into actively proliferating cells.We then evaluated IL-15SA's effects on anti-tumor activity against murine mastocytoma (P815) and murine B cell lymphoma (A20). IL-15SA enhanced graft-versus-tumor (GVT) activity in these tumors following T cell infusion. Interestingly, IL-15 SA administration provided GVT activity against A20 lymphoma cells in the murine donor leukocyte infusion (DLI) model without increasing graft versus host disease. In conclusion, IL-15SA could be a highly potent T- cell lymphoid growth factor and novel immunotherapeutic agent to complement stem cell transplantation and adoptive immunotherapy.

Indexed as

Adoptive TransferAnimalsAntineoplastic AgentsCell Line, TumorDisease Models, AnimalFemaleGraft vs Tumor EffectHematopoietic Stem Cell TransplantationInterleukin-15Interleukin-15 Receptor alpha SubunitLymphocyte CountMiceNeoplasmsProteinsRecombinant Fusion ProteinsT-Lymphocyte SubsetsALT-803Antineoplastic AgentsInterleukin-15Interleukin-15 Receptor alpha SubunitProteinsRecombinant Fusion Proteinsanimal modelscytokine therapygraft-versus-tumor activityinterleukin-15stem cell transplantation

Identifiers

PMID28574833
PMCPMC5546486

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Registered trials

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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.