lintuzumab   

GtoPdb Ligand ID: 7983

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 [4] 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 [2].
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 [1].
Mechanism Of Action and Pharmacodynamic Effects
CD33 is a transmembrane receptor expressed on cells of myeloid lineage [5]. After phosphorylation, CD33 is capable of recruiting the protein tyrosine phosphatases Src homology-2-containing tyrosine phosphatase-1 (SHP-1) and SHP-2 [7] and may function as an inhibitory receptor [8] by coligation with CD64 on myeloid cells [6]. Anti-CD33 monoclonal antibodies appear to function by blocking the differentiation of dendritic cells (DC) from monocytes and myeloid CD34+ precursors [12] by inducing apoptosis [3].