Evidence map›Paper›PMID 34247273›Full record

ArticleCancer immunology, immunotherapy : CII2022

Modulation of CD47-SIRPα innate immune checkpoint axis with Fc-function detuned anti-CD47 therapeutic antibody.

Rama Krishna Narla, Hardik Modi, Daniel Bauer, Mahan Abbasian, Jim Leisten, Joseph R Piccotti, Stephan Kopytek, Brendan P Eckelman, Quinn Deveraux, John Timmer and 5 more

2 registry-linked trialsOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer immunology, immunotherapy : CII, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.0field-weighted citation impact, top 13% 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.

NCT02367196 phase1completednot on this map

A Phase I, Open-Label, Dose Finding Study of CC-90002, a Monoclonal Antibody Directed Against CD47, in Subjects With Advanced Solid and Hematologic Cancers

TypeinterventionalSponsorCelgeneRan2015 to 2020Enrolled60ConditionsHematologic NeoplasmsArmsCC-90002, Rituximab
NCT02641002 phase1terminatednot on this map

A Phase 1, Open-label, Dose Finding Study of CC-90002, a Monoclonal Antibody Directed Against CD47, in Subjects With Acute Myeloid Leukemia and High-Risk Myelodsplastic Syndrome

TypeinterventionalSponsorCelgeneRan2016 to 2018Enrolled28ConditionsLeukemia, Myeloid, Acute, Myelodysplastic SyndromesArmsCC-90002
3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 31 citations in OpenAlex.

  1. Recent advances in the regulation of CD47 by non-coding RNAs and its therapeutic potential in cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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  3. Leveraging Macrophage Metabolic Reprogramming for Enhanced Anti-Tumor Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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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

15 authors at 3 institutions in 2 countries.

Rama Krishna NarlaBristol Myers Squibb, 10300 Campus Point Drive, Suite 100, San Diego, CA, 92121, USA. rama.narla@bms.com.ORCID http://orcid.org/0000-0001-5181-3376
Hardik ModiBristol Myers Squibb, 10300 Campus Point Drive, Suite 100, San Diego, CA, 92121, USA.
Daniel BauerBristol Myers Squibb, 10300 Campus Point Drive, Suite 100, San Diego, CA, 92121, USA.
Mahan AbbasianBristol Myers Squibb, 10300 Campus Point Drive, Suite 100, San Diego, CA, 92121, USA.
Jim LeistenBristol Myers Squibb, 10300 Campus Point Drive, Suite 100, San Diego, CA, 92121, USA.
Joseph R PiccottiBristol Myers Squibb, 10300 Campus Point Drive, Suite 100, San Diego, CA, 92121, USA.
Stephan KopytekBristol Myers Squibb, 10300 Campus Point Drive, Suite 100, San Diego, CA, 92121, USA.
Brendan P EckelmanInhibrx, San Diego, CA, USA.
Quinn DeverauxInhibrx, San Diego, CA, USA.
John TimmerInhibrx, San Diego, CA, USA.
Dan ZhuBristol Myers Squibb, 10300 Campus Point Drive, Suite 100, San Diego, CA, 92121, USA.
Lilly WongBristol Myers Squibb, 10300 Campus Point Drive, Suite 100, San Diego, CA, 92121, USA.
Laure EscoubetBristol Myers Squibb, 10300 Campus Point Drive, Suite 100, San Diego, CA, 92121, USA.
Heather K RaymonBristol Myers Squibb, 10300 Campus Point Drive, Suite 100, San Diego, CA, 92121, USA.
Kandasamy HariharanBristol Myers Squibb, 10300 Campus Point Drive, Suite 100, San Diego, CA, 92121, USA.
Bristol-Myers Squibb (United States) · USInhibrx (United States) · USBristol-Myers Squibb (Germany) · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cluster of differentiation 47 (CD47) is a transmembrane protein ubiquitously expressed on human cells but overexpressed on many different tumor cells. The interaction of CD47 with signal-regulatory protein alpha (SIRPα) triggers a "don't eat me" signal to the macrophage, inhibiting phagocytosis. Thus, overexpression of CD47 enables tumor cells to escape from immune surveillance via the blockade of phagocytic mechanisms. We report here the development and characterization of CC-90002, a humanized anti-CD47 antibody. CC-90002 is unique among previously reported anti-CD47 bivalent antibodies that it does not promote hemagglutination while maintaining high-affinity binding to CD47 and inhibition of the CD47-SIRPα interaction. Studies in a panel of hematological cancer cell lines showed concentration-dependent CC-90002-mediated phagocytosis in acute lymphoblastic leukemia, acute myeloid leukemia (AML), lenalidomide-resistant multiple myeloma (MM) cell lines and AML cells from patients. In vivo studies with MM cell line-derived xenograft models established in immunodeficient mice demonstrated significant dose-dependent antitumor activity of CC-90002. Treatment with CC-90002 significantly prolonged survival in an HL-60-disseminated AML model. Mechanistic studies confirmed the binding of CC-90002 to tumor cells and concomitant recruitment of F4-80 positive macrophages into the tumor and an increase in expression of select chemokines and cytokines of murine origin. Furthermore, the role of macrophages in the CC-90002-mediated antitumor activity was demonstrated by transient depletion of macrophages with liposome-clodronate treatment. In non-human primates, CC-90002 displayed acceptable pharmacokinetic properties and a favorable toxicity profile. These data demonstrate the potential activity of CC-90002 across hematological malignancies and provided basis for clinical studies CC-90002-ST-001 (NCT02367196) and CC-90002-AML-001 (NCT02641002).

Indexed as

AnimalsAntibodies, MonoclonalAntigens, DifferentiationAntineoplastic Agents, ImmunologicalApoptosisCD47 AntigenCell DifferentiationCell ProliferationFemaleHumansImmunoglobulin Fc FragmentsLeukemia, Promyelocytic, AcuteMacrophagesMiceMice, Inbred NODMice, SCIDAntibodies, MonoclonalAntigens, DifferentiationAntineoplastic Agents, ImmunologicalCD47 AntigenCD47 protein, humanImmunoglobulin Fc FragmentsReceptors, ImmunologicSIRPA protein, humanAMLCC-90002IgG4PEMacrophagesMultiple myelomaPhagocytosis

Identifiers

PMID34247273
PMCPMC10992396
OpenAlexW3177837228

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.