Target intelligence / Profile preview

Anti-DOTAM antibody (Anti-DOTAM)

Target
Anti-DOTAM
Molecular classification
Antibody, Immunoglobulin, Engineered protein
01

Overview

The DOTAM-binding antibody is an engineered immunoglobulin or antibody fragment designed to bind with high affinity to metal-chelate complexes of DOTAM (1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane). It is a central component of pre-targeted radioimmunotherapy (PRIT) systems, such as the DOTAM-PRIT platform developed for cancer treatment (Cheal et al., 2014, Molecular Cancer Therapeutics). In this therapeutic strategy, a bispecific antibody is first used to target a tumor-associated antigen (e.g., GPA33, CEA, or HER2), followed by the administration of a radiolabeled DOTAM hapten that is captured by the antibody at the tumor site (Orcutt et al., 2011, Protein Engineering, Design and Selection). This mechanism allows for high-contrast imaging and potent radiotherapy by separating the slow targeting phase from the fast delivery of the radionuclide, thereby minimizing systemic toxicity, particularly to the bone marrow (Zhou et al., 2015, Journal of Nuclear Medicine). The antibody itself is not a biological target but an artificial receptor created to facilitate the localization of diagnostic or therapeutic agents. Key challenges in its clinical application include the potential for immunogenicity and the optimization of the dosing interval between the antibody and the radioligand.

Other names
DOTAM-binding antibodyAnti-chelate antibodyAnti-DOTA antibodyC8252D12.5Anti-metal-DOTA antibodyAnti-hapten antibody
02

Mechanism of action

Pre-targeted capture of radiolabeled haptens for localized radiotherapy or imaging.

03

Biological functions

Hapten bindingMolecular capturePre-targeting
04

Disease associations

Cancer
05

Safety considerations

Immunogenicity (HAMA/HARA responses)Bone marrow toxicity from residual radioligandOff-target radiation exposureRenal clearance of radiolabeled haptens
06

Interacting drugs

Yttrium-90-DOTAM

4 more in the full profile.

07

Biomarkers

Tumor-associated antigen expression (e.g., GPA33, CEA, HER2)

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