CloneID: MLN591 (deJ591)
Antigen Long Description: The original antibody was raised by immunizing a mouse with human PMSA. The variable domain regions of mouse J591 were deimmunized by site-directed mutagenesis of putative T-cell reactive epitopes.
Buffer Composition: PBS only.
Uniprot Accession No.: Q04609
Specificity Statement: This antibody binds the extracellular domain of the human PSMA. Prostate-specific membrane antigen (PSMA) is a type II integral membrane glycoprotein belonging to the M28 peptidase family. It acts as a glutamate carboxypeptidase on different alternative substrate. It is highly expressed in cancerous cells and is used as an effective diagnostic and prognostic indicator of prostate cancer.
Application Notes (Clone): This antibody is the de-immunized version of anti-PSMA antibody J591. The radiolabelled version of this antibody was used for a radioimmunoassay on PMSA (US7514078B2). This antibody has been widely used for conjugation with drug maytansinoid 1 (DM1) a microtubule depolymerising agent, through thiopentanoate linker modification method of the antibody. The resulting immunoconjugate (MLN2704) contains 3-4 DM1 molecules per antibody. The immunoconjugate is a chemotherapeutic agent which effectively penetrates xenograft tumor tissue (PMID: 15520207). A phase I trials in patients with progressive, metastatic, castration-resistant prostate cancer investigated the safety profile, pharmacokinetics, immunogenicity, and preliminary antitumor activity of MLN2704. It was observed that the toxicity profile differs substantially from other PSMA-targeted therapies and is more typical of systemic chemotherapy, with nausea, fatigue, and diarrhea being the most commonly encountered adverse effects (PMID: 18362364). In the second study, using the yttrium-90-labeled deJ591-DOTA conjugate, with 61 progressive metastatic CRPC patients, most commonly encountered toxicities were also nausea, fatigue, and schedule-dependent neurotoxicity. Dose limiting toxicity was determined to be grade 3 transaminitis (PMID: 15173215). Another phase 1/2 study evaluated the dose-limiting toxicity and maximum tolerated dose of MLN2704. It reported that MLN2704 has limited activity in metastatic CRPC. Disulfide linker lability and rapid deconjugation lead to neurotoxicity and a narrow therapeutic window (PMID: 27765518). The DOTA labelled antibody was used for immunohistochemistry on human tissue. Here it showed specificity for prostate tissue. This antibody was used for an in vivo biodistribution experiment on nude mice. The uptake of this antibody by tumours was significantly higher than the control experiment. Furthermore the radiolabelled version of this antibody was used to treat mice with PMSA positive tumours. The labelled antibody was able to reduce mean tumour size by 80%-97%. The radiolabelled antibody was also tested in vivo in human. Here it showed that is targeted well to prostate cancer sites and it showed no toxic side effects in the patients. This antibody was also used for phase I and phase II trials where it showed some positive results (US7514078B2).
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