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Synonyms: ACTIMAB® | HuM195 | SGN-33 | SMART M195
Compound class: Antibody
Comment: Lintuzumab is a monoclonal antibody directed against CD33, a surface antigen found on myeloid leukemia cells. A modified version of lintuzumab that is conjugated with the chelator satetraxetan to facilitate actinium (225Ac) radiolabelling (a radioimmunotherapeutic) has been developed (see Patent US6670456  and IMGT/mAb-db ID 936). 225Ac emits α particles and is used as these cause less nonspecific cytotoxicity than β particles (i.e. decreased killing of bystander cells). 225Ac has been termed a 'nano-generator' as for each decay producing a high-energy α particle, a series of daughter atoms generate additional α particles, effectively amplifying the radioactive dose at the target site. Lintuzumab is a humanized version of the murine anti-CD33 antibody, M195 .
Ligand Activity Visualisation Charts
These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.✖
|No information available.|
|Summary of Clinical Use|
|A Phase 3 clinical trial (NCT00006045) is registerd with ClinicalTrials.gov, but its status has not been verified for more than two years. This study was investigating lintuzumab as a treatment for refractory or relapsed acute myelogenous leukemia. It appears that development of lintuzumab has been discontinued.
ACTIMAB-A®, the actinium (225Ac) lintuzumab satetraxetan radioimmunotherapeutic, was developed for newly diagnosed acute myeloid leukemia (AML) patients, and is in Phase 1/2 trial .
|Mechanism Of Action and Pharmacodynamic Effects|
|CD33 is a transmembrane receptor expressed on cells of myeloid lineage . After phosphorylation, CD33 is capable of recruiting the protein tyrosine phosphatases Src homology-2-containing tyrosine phosphatase-1 (SHP-1) and SHP-2  and may function as an inhibitory receptor  by coligation with CD64 on myeloid cells . Anti-CD33 monoclonal antibodies appear to function by blocking the differentiation of dendritic cells (DC) from monocytes and myeloid CD34+ precursors  by inducing apoptosis .|