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BIOMARKER:

IL3RA positive

i
Other names: IL3RA, Interleukin 3 Receptor Subunit Alpha, CD123, Interleukin 3 Receptor, Alpha (Low Affinity), Interleukin-3 Receptor Subunit Alpha, IL-3 Receptor Subunit Alpha, IL-3R Subunit Alpha, CD123 Antigen, IL-3R-Alpha, IL3R, HIL-3Ra, IL3RAY, IL-3RA, IL3RX, IL3RY
Entrez ID:
Related biomarkers:
1m
BRD4 inhibitor reduces exhaustion and blocks terminal differentiation in CAR-T cells by modulating BATF and EGR1. (PubMed, Biomark Res)
Our study reveals that a BRD4 inhibitor can reduce CAR-T cell exhaustion and block exhausted T cell terminal differentiation by downregulating BATF activity and expression together with upregulating EGR1 activity and expression, presenting an approach for improving the effectiveness of CAR-T cell therapy.
Journal • CAR T-Cell Therapy • IO biomarker
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CD8 (cluster of differentiation 8) • CD123 (Interleukin 3 Receptor Subunit Alpha) • BRD4 (Bromodomain Containing 4) • IL3RA (Interleukin 3 Receptor Subunit Alpha) • BATF (Basic Leucine Zipper ATF-Like Transcription Factor) • EGR1 (Early Growth Response 1)
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IL3RA positive
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JQ-1
1m
New P1 trial
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IL3RA (Interleukin 3 Receptor Subunit Alpha)
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CD123 positive • IL3RA positive
2ms
Enrollment open
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IL3RA (Interleukin 3 Receptor Subunit Alpha)
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CD123 positive • IL3RA positive
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AFM28
7ms
Clinical Characteristics of CD4-CD56+ Blastic Plasmacytoid Dendritic Cell Neoplasm (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)
CD4-CD56+ BPDCN is very rare and easily misdiagnosed as other hematological tumors with poor prognosis. Acute lymphoblastic leukemia or lymphomatoid therapy should be used first to improve the poor prognosis.
Retrospective data • Journal
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CD20 (Membrane Spanning 4-Domains A1) • CD123 (Interleukin 3 Receptor Subunit Alpha) • CD34 (CD34 molecule) • CD4 (CD4 Molecule) • NCAM1 (Neural cell adhesion molecule 1) • IL3RA (Interleukin 3 Receptor Subunit Alpha) • NRP1 (Neuropilin 1)
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CD20 positive • IL3RA positive
7ms
Bortezomib suppresses acute myelogenous leukaemia stem-like KG-1a cells via NF-κB inhibition and the induction of oxidative stress. (PubMed, J Cell Mol Med)
BTZ also increased mitochondrial superoxide levels in KG-1a cells, and BTZ-induced apoptosis was partially prevented by pretreatment with the antioxidant N-acetylcysteine, indicating that BTZ induces oxidative stress-mediated apoptosis in KG-1a cells. At a dosage of 0.1 mg/kg every other day for 2 weeks, BTZ significantly reduced the percentage of hCD45-positive cells in the bone marrow and peripheral blood of NSG mice engrafted with KG-1a cells with tolerable toxicity. Taken together, these data indicate that the anti-LSC potential of BTZ appears to be an important strategy for AML treatment.
Journal
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CD123 (Interleukin 3 Receptor Subunit Alpha) • CD34 (CD34 molecule) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • CASP3 (Caspase 3) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
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CD123 positive • CD34 positive • IL3RA positive
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bortezomib
7ms
IMGN632-0802: IMGN632 as Monotherapy or With Venetoclax and/or Azacitidine for Participants With CD123-Positive Acute Myeloid Leukemia (clinicaltrials.gov)
P1/2, N=218, Active, not recruiting, ImmunoGen, Inc. | Recruiting --> Active, not recruiting | Phase classification: P1b/2 --> P1/2
Enrollment closed • Phase classification
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IL3RA (Interleukin 3 Receptor Subunit Alpha)
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CD123 positive • IL3RA positive
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Venclexta (venetoclax) • azacitidine • decitabine • pivekimab sunirine (IMGN632)
7ms
Flotetuzumab as a salvage immunotherapy in advanced CD123-positive hematological malignancies, a phase 1 pilot study. (PubMed, Leuk Lymphoma)
Responses only occurred in Cohort B, with a partial response in one patient with Hodgkin's lymphoma and morphological complete remission in the bone marrow in one patient with blastic plasmacytoid dendritic cell neoplasm. In conclusion, flotetuzumab had a manageable safety profile in advanced CD123-positive hematological malignancies.
P1 data • Journal • IO biomarker • Metastases
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CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
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CD123 positive • CD123 expression • IL3RA expression • IL3RA positive
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flotetuzumab (MGD006)
7ms
Tagraxofusp, a first-in-class CD123-targeted agent: Five-year postapproval comprehensive review of the literature. (PubMed, Cancer)
The successful targeting of CD123 in BPDCN has also encouraged research into a variety of other CD123-positive hematological neoplasms, including acute myeloid leukemia (AML), and informed the development of other novel agents targeting CD123. This review examines the clinical data leading to the development and approval of tagraxofusp in BPDCN, how it is being used in combination to improve outcomes in BPDCN and AML, and its developing role in other hematological malignancies.
Review • Journal
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CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
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CD123 positive • IL3RA positive
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Elzonris (tagraxofusp-erzs)
8ms
Pivekimab sunirine (IMGN632), a novel CD123-targeting antibody-drug conjugate, in relapsed or refractory acute myeloid leukaemia: a phase 1/2 study. (PubMed, Lancet Oncol)
Pivekimab sunirine showed single-agent activity across multiple doses, with a recommended phase 2 dose of 0·045 mg/kg once every 3 weeks. These findings led to a phase 1b/2 study of pivekimab sunirine plus azacitidine and venetoclax in patients with CD123-positive acute myeloid leukaemia.
P1/2 data • Clinical Trial,Phase II • Journal
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CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
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CD123 positive • CD123 expression • IL3RA expression • IL3RA positive
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Venclexta (venetoclax) • azacitidine • pivekimab sunirine (IMGN632)
12ms
Phase 1b trial of tagraxofusp in combination with azacitidine with or without venetoclax in acute myeloid leukemia. (PubMed, Blood Adv)
Median overall survival and progression-free survival were 14 months (95% CI, 9.5-NA) and 8.5 months (95% CI, 5.1-NA), respectively. In summary, TAG-AZA-VEN shows encouraging safety and activity in high-risk AML, including TP53-mutated disease, supporting further clinical development of TAG combinations.
P1 data • Journal • Combination therapy • IO biomarker
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TP53 (Tumor protein P53) • CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
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TP53 mutation • CD123 positive • IL3RA positive
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Venclexta (venetoclax) • azacitidine • Elzonris (tagraxofusp-erzs)
12ms
Tagraxofusp Shows Promising Anti-Tumoral Efficacy in Preclinical in Vitro Models of Myelofibrosis, Both As a Single Agent and in Combination with Janus Kinase Inhibitors (ASH 2023)
The role of the JAK/Signal transducer and activator of transcriptions (STAT) pathway in MF has led to the recent approval of three different JAK2 inhibitors (ruxolitinib, pacritinib, and fedratinib) for MF treatment. Our studies showed high sensitivity of MF cell lines to tagraxofusp as a single agent, which is expected given phase 2 results demonstrated clinical efficacy of single-agent tagraxofusp in R/R MF (Yacoub et al. ASH 2021). In addition, synergism was observed in combination with JAK inhibitors.
Preclinical • Combination therapy
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CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
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CD123 positive • JAK2 V617F • CD123 expression • IL3RA expression • IL3RA positive
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Jakafi (ruxolitinib) • Elzonris (tagraxofusp-erzs) • Vonjo (pacritinib) • Inrebic (fedratinib)
12ms
Diagnostic Challenges in the Leukemia Phase of Blastic Plasmacytoid Dendritic Cell Neoplasm without Skin Involvement: A Clinical and Pathological Study (ASH 2023)
Only one cycle of decitabine + CAG was given and 5 months later, the disease progressed to the leukemia phase...The latter case had ASXL1 and TET2 mutations detected by NGS analysis, achieved complete remission after receiving venetoclax + azacitidine for one cycle, followed by intermittent venoclax +demethylation agent or low-dose chemotherapy maintenance treatment and live for more than two years now... BPDCN without skin lesions is clinically rare, and its diagnosis is challenging. Comprehensive immunophenotyping and cautious interpretation of immunohistochemistry results such as dim lysozyme expression are crucial. Venetoclax-containing regimens have shown promising therapeutic effects.
Clinical
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TP53 (Tumor protein P53) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CD20 (Membrane Spanning 4-Domains A1) • CD8 (cluster of differentiation 8) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • CD123 (Interleukin 3 Receptor Subunit Alpha) • CD33 (CD33 Molecule) • CD34 (CD34 molecule) • CD36 (thrombospondin receptor) • NCAM1 (Neural cell adhesion molecule 1) • CD5 (CD5 Molecule) • CD14 (CD14 Molecule) • ITGAM (Integrin, alpha M) • MME (Membrane Metalloendopeptidase) • CD7 (CD7 Molecule) • IL3RA (Interleukin 3 Receptor Subunit Alpha) • NRP1 (Neuropilin 1) • SPN (Sialophorin) • TCL1A (TCL1 Family AKT Coactivator A) • ANPEP (Alanyl Aminopeptidase, Membrane) • CLEC4C (C-Type Lectin Domain Family 4 Member C) • MPO (Myeloperoxidase)
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TP53 mutation • ASXL1 mutation • TET2 mutation • CD123 positive • NCAM1 expression • CD123 expression • CD4 expression • IDH2 mutation + TP53 mutation • IL3RA positive • NCAM1 positive
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Venclexta (venetoclax) • azacitidine • decitabine
12ms
First Disclosure of AZD9829, a TOP1i-ADC Targeting CD123: Promising Preclinical Activity in AML Models with Minimal Effect on Healthy Progenitors (ASH 2023)
Furthermore, AZD9829 demonstrated durable blast reduction at day 28 after the first dose with leukemic blast reduction in blood (7/13 models) and in bone marrow (5/13 models). Safety studies in cynomolgus monkey support the clinical development of AZD9829, a promising therapeutic candidate for the treatment of AML across the spectrum of CD123-expression and genetic mutations.
Preclinical
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CD123 (Interleukin 3 Receptor Subunit Alpha) • CD33 (CD33 Molecule) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
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CD123 positive • CD123 expression • IL3RA expression • IL3RA positive
12ms
Plasmacytoid Dendritic Cells, the Expression of the Stimulator of Interferon Genes Protein (STING) and a Possible Role of Th17 Immune Response in Cervical Lesions Mediated by Human Papillomavirus. (PubMed, Indian J Microbiol)
Cells expressing IL17 were present in three groups, more frequent in cervicitis. Considering that the casuistic is composed of women carrying HIV, this infectious agent could influence the numerical similarities of the cells studied among three groups, even in the absence of HPV.
Journal
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CD123 (Interleukin 3 Receptor Subunit Alpha) • STING (stimulator of interferon response cGAMP interactor 1) • FOXP3 (Forkhead Box P3) • IL17A (Interleukin 17A) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
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CD123 expression • IL3RA positive
12ms
Trial completion date • Trial primary completion date
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IL3RA (Interleukin 3 Receptor Subunit Alpha)
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CD123 positive • IL3RA positive
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AFM28
almost1year
IRF8 in Conjunction With CD123 and CD20 to Distinguish Lupus Erythematosus Panniculitis From Subcutaneous Panniculitis-like T-Cell Lymphoma. (PubMed, Am J Surg Pathol)
However, a panel combining IRF8, CD123, and CD20, with at least 1 positive marker was more accurate than any individual marker by receiver operating characteristic curve analysis. Our study provides a rationale for potentially including IRF8 as part of an immunohistochemical panel composed of other currently available markers used to differentiate LEP from SPTCL.
Journal
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CD20 (Membrane Spanning 4-Domains A1) • CD123 (Interleukin 3 Receptor Subunit Alpha) • IRF8 (Interferon Regulatory Factor 8) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
CD123 positive • CD123 expression • IL3RA positive • IRF8 expression
1year
Venetoclax Synergizes with IMGN632, a Novel CD123-Targeting Antibody Conjugated to a DNA Alkylating Payload, By Suppressing DNA Damage Response and Potentiating Apoptosis in Acute Myeloid Leukemia in Vitro Models (ASH 2023)
Importantly, we previously showed high synergy of IMGN632 combination with BCL-2 inhibitor venetoclax (VEN) and DNA hypomethylating azacytidine (AZA) in AML cell lines and xenograft models (ASH 2020, #617). Together, these results suggest that VEN, apart from its canonical inhibitory effect on anti-apoptotic BCL-2, exerts previously unrecognized ability to suppress DDR program in AML and augments activity of DNA damaging IMGN632. Failure of cells to sustain DDR in the presence of VEN constitutes a key aspect of high efficacy of IMGN/VEN/AZA combination in AML.
Preclinical • PARP Biomarker • IO biomarker
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FLT3 (Fms-related tyrosine kinase 3) • MCL1 (Myeloid cell leukemia 1) • CD123 (Interleukin 3 Receptor Subunit Alpha) • CHEK1 (Checkpoint kinase 1) • CASP3 (Caspase 3) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
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FLT3-ITD mutation • FLT3 mutation • CD123 positive • MCL1 expression • IL3RA positive
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Venclexta (venetoclax) • azacitidine • pivekimab sunirine (IMGN632)
1year
First-in-Human Study of the CD123 NK Cell Engager SAR443579 in Relapsed or Refractory Acute Myeloid Leukemia, B-Cell Acute Lymphoblastic Leukemia or High Risk-Myelodysplasia: Updated Safety, Efficacy, Pharmacokinetics and Pharmacodynamics (ASH 2023)
Pts had received a median of 2.0 (1.0 –10.0) prior lines of treatment with 13 pts (30.2%) reporting prior hematopoietic stem cell transplantation and 36 pts (83.7%) with prior exposure to venetoclax. SAR'579 was well tolerated up to doses of 6000 µg/kg QW with observed clinical benefit in pts with R/R AML. The results are consistent with the predicted favorable safety profile.
Clinical • P1 data • PK/PD data
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CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
CD123 positive • IL3RA positive
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Venclexta (venetoclax) • SAR443579
1year
Pivekimab Sunirine (PVEK, IMGN632), a CD123-Targeting Antibody-Drug Conjugate, in Combination with Azacitidine and Venetoclax in Patients with Newly Diagnosed Acute Myeloid Leukemia (ASH 2023)
Encouraging CCRMRD- rates were observed across cytogenetic/molecular subsets, and the majority of responding pts achieved early and deep remissions, which may translate to improved clinical outcomes. The regimen was well tolerated with no new safety signals, and the addition of PVEK to the AZA-VEN backbone did not appear to meaningfully prolong count recovery.
Clinical • Combination therapy
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FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
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TP53 wild-type • CD123 positive • CD123 expression • IL3RA expression • IL3RA positive
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Venclexta (venetoclax) • azacitidine • pivekimab sunirine (IMGN632)
1year
Potent in Vitro and In Vivo Efficacy of BYON4413, a Duba-Based Antibody-Drug Conjugate Targeting CD123 in Acute Myeloid Leukemia (ASH 2023)
In sum, BYON4413 shows great potential to be an effective targeted therapy against AML, MDS, and other CD123+ hematological malignancies such as blastic plasmacytoid dendritic cell neoplasm (BPDCN). Readied with these promising pre-clinical results, we have designed a first-in-human dose-escalation and expansion trial enrolling AML and high-risk MDS patients scheduled to begin in Q12024.
Preclinical
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CD123 (Interleukin 3 Receptor Subunit Alpha) • CD34 (CD34 molecule) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
CD123 positive • CD123 expression • IL3RA positive
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BYON4413
1year
Functional Characterization and Optimization of Switchable Allogeneic Chimeric Antigen Receptor T Cells for Targeting CD19 and CD20 in B Cell Malignancies (ASH 2023)
A summary of functional characterization data will be presented at the meeting with a focus on the lack of predictability of certain in vitro models and underlying hypotheses. Insights from these studies are now flowing into preclinical development of a novel switchable allogeneic CAR-T cell product candidate targeting CD19 and CD20 in B cell malignancies engineered to fully overcome graft-versus-host disease as well as graft rejection by host T and NK cells.
CAR T-Cell Therapy
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CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
CD123 positive • IL3RA positive
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AVC-201
1year
Tagraxofusp in myeloid malignancies. (PubMed, Hematol Oncol)
The triplet tagraxofusp-azacytidine-venetoclax appears to be of particular interest among these combinations. Nowadays, several ongoing trials are exploring the use of tagraxofusp in different myeloid neoplasms. This review aims to summarize the actual role of tagraxofusp in BPDCN and other CD123-positive myeloid malignancies.
Review • Journal
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CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
CD123 positive • IL3RA positive
|
Venclexta (venetoclax) • azacitidine • Elzonris (tagraxofusp-erzs)
1year
Hairy Cell Leukemia: Hematological and Immunophenotypic Profile of 13 Patients. (PubMed, Cureus)
The diagnosis of HCL requires a multipronged approach. The use of clinical features, morphology, and immunophenotyping combined with ancillary techniques provides higher diagnostic accuracy and enables its distinction from other B-cell lymphoproliferative disorders (BCLPDs), leading to better patient management and treatment.
Journal
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CD20 (Membrane Spanning 4-Domains A1) • CD123 (Interleukin 3 Receptor Subunit Alpha) • CD22 (CD22 Molecule) • IL2RA (Interleukin 2 receptor, alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha) • ITGAE (Integrin Subunit Alpha E) • ITGAX (Integrin Subunit Alpha X) • ISG20 (Interferon Stimulated Exonuclease Gene 20)
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CD123 positive • CD22 expression • IL3RA positive
1year
IMGN632 as Monotherapy or With Venetoclax and/or Azacitidine for Participants With CD123-Positive Acute Myeloid Leukemia (clinicaltrials.gov)
P1b/2, N=292, Recruiting, ImmunoGen, Inc. | Trial completion date: Jun 2024 --> Dec 2024 | Trial primary completion date: Jun 2024 --> Dec 2024
Trial completion date • Trial primary completion date
|
CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
CD123 positive • IL3RA positive
|
Venclexta (venetoclax) • azacitidine • decitabine • pivekimab sunirine (IMGN632)
1year
Tandem bispecific CD123/CLL-1 CAR-T cells exhibit specific cytolytic effector functions against human acute myeloid leukaemia. (PubMed, Eur J Haematol)
CD123/CLL-1 CAR-T cells in tandem can simultaneously target CD123 and CLL-1 on AML cells, demonstrating a significant ability to kill single antigens and multi-target tumour cells. This suggests that CD123/CLL-1 CAR-T cells exhibit significant advantages in the expression of multiple antigens in a wide range of target cells, which may help overcome the challenges posed by tumour heterogeneity and evasion mechanisms.
Journal • CAR T-Cell Therapy • IO biomarker
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CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
CD123 expression • IL3RA positive
1year
A Study of the Drug IMGN632 in Children With Leukemia That Has Come Back After Treatment or is Difficult to Treat (clinicaltrials.gov)
P1/2, N=0, Withdrawn, Children's Oncology Group | N=38 --> 0 | Not yet recruiting --> Withdrawn
Enrollment change • Trial withdrawal
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IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
CD123 positive • IL3RA positive
|
methotrexate • Vyxeos (cytarabine/daunorubicin liposomal formulation) • fludarabine IV • pivekimab sunirine (IMGN632) • Starasid (cytarabine ocfosfate)
1year
New P1/2 trial
|
IL6 (Interleukin 6) • CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
CD123 positive • CD123 expression • IL3RA positive
|
cyclophosphamide • CD123 targeted CAR-NK
over1year
IMGN632 as Monotherapy or With Venetoclax and/or Azacitidine for Participants With CD123-Positive Acute Myeloid Leukemia (clinicaltrials.gov)
P1b/2, N=242, Recruiting, ImmunoGen, Inc. | Trial completion date: Jun 2022 --> Jun 2024 | Trial primary completion date: Jun 2022 --> Jun 2024
Trial completion date • Trial primary completion date
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CD123 (Interleukin 3 Receptor Subunit Alpha) • IL3RA (Interleukin 3 Receptor Subunit Alpha)
|
CD123 positive • IL3RA positive
|
Venclexta (venetoclax) • azacitidine • decitabine • pivekimab sunirine (IMGN632)