Evidence map›Paper›PMID 9990069›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America1999

Synergy between an antiangiogenic integrin alphav antagonist and an antibody-cytokine fusion protein eradicates spontaneous tumor metastases.

H N Lode, T Moehler, R Xiang, A Jonczyk, S D Gillies, D A Cheresh, R A Reisfeld

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
10.3field-weighted citation impact, top 1% 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

28 citing papers in PubMed, 127 citations in OpenAlex.

  1. Trial
  2. Article
  3. Interaction of integrin αFrontiers in cell and developmental biology · 2025
    Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. PPARgamma in Neuroblastoma.PPAR research · 2008
    Article
  18. Article
  19. Integrins: molecular targets in cancer therapy.Current oncology reports · 2006
    Review
  20. Clinical implications of angiogenesis in cancers.Vascular health and risk management · 2006
    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

7 authors at 2 institutions in 2 countries.

H N LodeThe Scripps Research Institute, Department of Immunology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
T Moehler
R Xiang
A Jonczyk
S D Gillies
D A Cheresh
R A Reisfeld
Merck (Germany) · DEScripps Research Institute · US

Funding

REGULATION OF TUMOR CELL ATTACHMENT BY SURFACE ANTIGENSR01CA045726 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHERESH, DAVID A · 1988 to 2017
$7.4M
VEGF and PDGF in angiogenesis and tumor progressionR37CA050286 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHERESH, DAVID A · 1999 to 2013
$6.3M
STRUCTURAL AND FUNCTIONAL STUDIES--INTEGERIN-DEPENDENTR01CA050286 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHERESH, DAVID A · 1989 to 2018
$1.9M
MOLECULAR PROFILE OF MELANOMA AND NEUROBLASTOMA ANTIGENSR35CA042508 · NCI · SCRIPPS RESEARCH INSTITUTE · PI LODE, HOLGER N · 1986 to 2000
$70k
NCI NIH HHS CA-42508NCI NIH HHS CA-45726NCI NIH HHS CA-50286NCI NIH HHS R01 CA045726NCI NIH HHS R01 CA050286NCI NIH HHS R37 CA050286
6 · The paper itself

Abstract

The suppression and eradication of primary tumors and distant metastases is a major goal of alternative treatment strategies for cancer, such as inhibition of angiogenesis and targeted immunotherapy. We report here a synergy between two novel monotherapies directed against vascular and tumor compartments, respectively, a tumor vasculature-specific antiangiogenic integrin alphav antagonist and tumor-specific antibody-interleukin 2 (IL-2) fusion proteins. Simultaneous and sequential combination of these monotherapies effectively eradicated spontaneous liver metastases in a poorly immunogenic syngeneic model of neuroblastoma. This was in contrast to controls subjected to monotherapies with either an antiangiogenic integrin alphav antagonist or antibody-IL-2 fusion proteins, which were only partially effective at the dose levels applied. Furthermore, simultaneous treatments with the integrin alphav antagonist and tumor-specific antibody-IL-2 fusion proteins induced dramatic primary tumor regressions in three syngeneic murine tumor models, i.e., melanoma, colon carcinoma, and neuroblastoma. However, each agent used as monotherapy induced only a delay in tumor growth. A mechanism for this synergism was suggested because the antitumor response was accompanied by a simultaneous 50% reduction in tumor vessel density and a 5-fold increase in inflammatory cells in the tumor microenvironment. Subsequently, tumor necrosis was demonstrated only in animals receiving the combination therapy, but not when each agent was applied as monotherapy. The results suggest that these synergistic treatment modalities may provide a novel and effective tool for future therapies of metastatic cancer.

Indexed as

AnimalsAntigens, CDColonic NeoplasmsHumansImmunotherapyImmunotoxinsIntegrin alphaVInterleukin-2Melanoma, ExperimentalMiceNeoplasm MetastasisNeovascularization, PathologicNeuroblastomaPeptides, CyclicReceptors, VitronectinRecombinant Fusion ProteinsAntigens, CDCilengitideImmunotoxinsIntegrin alphaVInterleukin-2Peptides, CyclicReceptors, VitronectinRecombinant Fusion ProteinsSnake Venoms

Identifiers

PMID9990069
PMCPMC15528
OpenAlexW2008181555

What OpenQuestion holds

Textmetadata
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.