Evidence map›Paper›PMID 33218169›Full record

ArticleInternational journal of molecular sciences2020

Mechanistic Insights into Synergy between Melanin-Targeting Radioimmunotherapy and Immunotherapy in Experimental Melanoma.

Mackenzie E Malo, Kevin J H Allen, Rubin Jiao, Connor Frank, David Rickles, Ekaterina Dadachova

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
1.4field-weighted citation impact, top 15% of its field
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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Review
  10. Review
  11. Review
  12. Combined Targeted Radiopharmaceutical Therapy and Immune Checkpoint Blockade: From Preclinical Advances to the Clinic.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2022
    Article
  13. Combining Targeted Radionuclide Therapy and Immune Checkpoint Inhibition for Cancer Treatment.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
    Review
  14. Targeting Melanin in Melanoma with Radionuclide Therapy.International journal of molecular sciences · 2022
    Review
  15. Article
  16. Assessment ofJournal of medical physics
    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

6 authors at 1 institution in 1 country.

Mackenzie E MaloCollege of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.ORCID 0000-0002-9118-0806
Kevin J H AllenCollege of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
Rubin JiaoCollege of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
Connor FrankCollege of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
David RicklesRadImmune Therapeutics Inc., Burlingame, CA 94010, USA.
Ekaterina DadachovaCollege of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
University of Saskatchewan · CA

Funding

RadImmune Therapeutics, Inc., USA N/ASylvia Fedoruk Center for Nuclear Innovation 421562
6 · The paper itself

Abstract

Melanoma incidence continues to rise, and while therapeutic approaches for early stage cases are effective, metastatic melanoma continues to be associated with high mortality. Immune checkpoint blockade (ICB) has demonstrated clinical success with approved drugs in cohorts of patients with metastatic melanoma and targeted radionuclide therapy strategies showed promise in several clinical trials against various cancers including metastatic melanoma. This led our group to investigate the combination of these two treatments which could be potentially offered to patients with metastatic melanoma not responsive to ICB alone. Previously, we have demonstrated that a combination of humanized anti-melanin antibody conjugated to 213Bismuth and anti-PD-1 ICB reduced tumor growth and increased survival in the Cloudman S91 murine melanoma DBA/2 mouse model. In the current study, we sought to improve the tumoricidal effect by using the long-lived radionuclides 177Lutetium and 225Actinium. Male Cloudman S91-bearing DBA/2 mice were treated intraperitoneally with PBS (Sham), unlabeled antibody to melanin, anti-PD-1 ICB, 177Lutetium or 225Actinium RIT, or a combination of ICB and RIT. Treatment with anti-PD-1 alone or low-dose 177Lutetium RIT alone resulted in modest tumor reduction, while their combination significantly reduced tumor growth and increased survival, suggesting synergy. 225Actinium RIT, alone or in combination with ICB, showed no therapeutic benefit, suggesting that the two radionuclides with different energetic properties work in distinct ways. We did not detect an increase in tumor-infiltrating T cells in the tumor microenvironment, which suggests the involvement of alternative mechanisms that improve the effect of combination therapy beyond that observed in the single therapies.

Indexed as

AnimalsCell Line, TumorCombined Modality TherapyHumansImmune Checkpoint InhibitorsImmunoconjugatesImmunotherapyMaleMelaninsMelanoma, ExperimentalMice, Inbred DBARadioimmunotherapySurvival AnalysisTreatment OutcomeTumor BurdenImmune Checkpoint InhibitorsImmunoconjugatesMelaninsactinium-225anti-PD-1 immunotherapyDBA/2 micelutetium-177radioimmunotherapy

Identifiers

PMID33218169
PMCPMC7698872
OpenAlexW3103787729

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.