Acute lymphocytic leukemia (ALL)

Disease ID:1172
Name:Acute lymphocytic leukemia (ALL)
Associated with:3 targets
2 immuno-relevant targets
2 immuno-relevant ligands
Synonyms
Acute lymphoblastic leukemia
Description
ALL is a subtype of acute leukemia
Database Links
OMIM: 613065

Targets

CD3e
Comments:  CD3e is the molecular target of approved drug blinatumomab, as a treatment Philadelphia chromosome-negative precursor B-cell ALL
Ligand interactions: 
Ligand Comments
blinatumomab
Approved specifically for Philadelphia chromosome-negative precursor B-cell acute lymphoblastic leukemia (B-cell ALL), an uncommon form of ALL.
CD19
Comments:  CD19 is one of the molecular targets of the bi-specific antibody drug blinatumomab (also binds CD3e).
Ligand interactions: 
Ligand Comments
blinatumomab
Approved specifically for Philadelphia chromosome-negative precursor B-cell acute lymphoblastic leukemia (B-cell ALL), an uncommon form of ALL.
regulator of G-protein signaling 1
References:  2

Ligands

Key to terms and symbols Click ligand name to view ligand summary Click column headers to sort
Ligand References Clinical comments
inotuzumab ozogamicin
Immuno Disease Comments: Approved therapy for ALL.
Clinical Use: The EMA has granted inotuzumab ozogamicin orphan designation for the treatment of the rare disease B-cell acute lymphoblastic leukemia (ALL).
Although Phase 3 clinical trials assessing inotuzumab ozogamicin as a treatment for non-Hodgkin lymphoma have been terminated (NCT01232556 and NCT00562965) because they were unlikely to meet their primary objective of improving overall survival (OS), a separate Phase 3 trial in patients with ALL is ongoing (NCT01564784). Preliminary results from this ALL trial indicated extended progression-free and overall survival with inotuzumab ozogamicin compared to standard therapy [3]. The FDA granted breakthrough therapy designation for inotuzumab ozogamicin for ALL based on these results. The EMA had granted orphan designation for ALL in 2013. Both the EMA and FDA converted to full approval as a treatment for ALL in 2017. Veno-occlusive liver disease was observed as a major adverse event associated with inotuzumab ozogamicin therapy. | View clinical data
blinatumomab
Immuno Disease Comments: Approved specifically for Philadelphia chromosome-negative precursor B-cell acute lymphoblastic leukemia (B-cell ALL), an uncommon form of ALL.
Clinical Use: In December 2014 the FDA approved blinatumomab for use in the treatment of Philadelphia chromosome-negative (Ph-) precursor B-cell acute lymphoblastic leukemia (B-cell ALL), an uncommon form of ALL. Blinatumomab is undergoing clinical trial for other forms of ALL and lymphoma. A list of current trials can be viewed at ClinicalTrials.gov. In the European Union blinatumomab is a EMA designated orphan drug that can be used to treat Ph- relapsed or refractory B-cell precursor ALL.
In July 2017, the FDA expanded approval to include treatment of relapsed or refractory B-cell precursor ALL in adults and children, based on data from the Phase 3 TOWER study that shows that blinatumomab single agent therapy exhibits superior improvement in median overall survival over standard of care chemotherapy. This is the first single-agent immunotherapy approved to treat patients with Ph- relapsed or refractory B-cell precursor ALL. March 2018 saw FDA approval expanded further to include treatment of adult and pediatric patients with B-cell precursor ALL in first or second complete remission with minimal residual disease (MRD), based on the BLAST trial (NCT01207388) [1]. | View clinical data
Bioactivity Comments: The development of blinatumomab is covered by patent US7635472 [4], based on peptide sequence matches of the two antigen-binding variable heavy chains regions of blinatumomab. In this patent specificity and efficacy of blinatumomab binding was determined by FACS analysis and ELISA. However, the specific clone producing blinatumomab is not reported, nor are binding affinity values for antibody-antigen interactions | View biological activity

References

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1. Gökbuget N, Dombret H, Bonifacio M, Reichle A, Graux C, Faul C, Diedrich H, Topp MS, Brüggemann M, Horst HA et al.. (2018) Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood, 131 (14): 1522-1531. [PMID:29358182]

2. Hong JX, Wilson GL, Fox CH, Kehrl JH. (1993) Isolation and characterization of a novel B cell activation gene. J. Immunol., 150 (9): 3895-904. [PMID:8473738]

3. Kantarjian HM, DeAngelo DJ, Stelljes M, Martinelli G, Liedtke M, Stock W, Gökbuget N, O'Brien S, Wang K, Wang T et al.. (2016) Inotuzumab Ozogamicin versus Standard Therapy for Acute Lymphoblastic Leukemia. N. Engl. J. Med., 375 (8): 740-53. [PMID:27292104]

4. Kufer P, Lutterbuse R, Kohleisen B, Zeman S, Bauerle P. (2009) Single chain antibody construct comprising binding domains specific for human CD3 and human CD19. Patent number: US7635472. Assignee: Micromet Ag. Priority date: 31/05/2003. Publication date: 22/12/2009.