Immunoconjugate

An immunoconjugate "( interchangeably antibody conjugate ) refers to an antibody, an antibody fragment or antibody mimetic that through a covalent bond (conjugation ) is connected to a second functional molecule as a molecular marker. The second functional molecule can be, for example, a reporter enzyme, a drug, a radionuclide or a fluorescent label.

Operation

Immunoconjugates are used in biochemistry for immune labeling of biomolecules, or in the treatment of cancer as Chemoimmunkonjugate (synonym antibody-drug conjugate). The coupling of a molecule to the antibody takes place in the course of a molecular marker. By means of the antibody, antibody fragment or antibody mimetic, a selective binding to a specific target structure ( target) is a cell or a molecule obtained. This may be, for example, a tumor cell that presents on its surface a specific antigen. The conjugated functional molecule may - in the case of therapeutic applications - for example, be a toxin, which can exert a cytotoxic effect at its destination. By (ideally) selective binding to the target structure, the active ingredient is released only at the desired location. Healthy cells are largely spared. It is a special form of the drug targeting.

In therapeutic use may also be radionuclides, such as 90Yttrium, a β - emitters are used. In this case, one also speaks of radioimmunoconjugates, or of radioimmunotherapy. Radionuclides are bound most strong complexing agents, such as DOTA, DTPA or TTHA to the antibody. The short range of β - radiation causes only cells can be damaged in the immediate vicinity of the immunoconjugates.

Radioimmunoconjugates but can also be used for purely diagnostic purposes. In these cases, short-lived strong γ - emitters, such as 99mTechnetium, for the single - photon emission computed tomography or positron emitters such as 68Gallium for positron emission tomography ( " immuno- PET" ) are conjugated to antibodies via complexing. Thus, the course of therapy and, where appropriate Metastatisierungen can be tracked or diagnosed in patients, for example. Also in the field of diagnostic conjugates of fluorescent dyes with antibodies can be used. These immunoconjugates are mainly used in preclinical studies and for pure research purposes. Radiolabeled antibodies can also be used in a radioimmunoassay.

In the biochemical analysis reporter enzyme-linked immunoconjugates in different detection methods are used for signal amplification (eg, ELISA, ELISPOT, Western blot and immunohistochemistry), in part as a double immunolabeling.

By a fluorescent label modified antibodies used in the immunofluorescence microscopy, fluorometry, and flow cytometry.

Are cytokines linked to an antibody or an antibody fragment, it is called a immunocytokine.

Examples

Gemtuzumab ozogamicin is approved in the United States for the treatment of acute myeloid leukemia from a immunoconjugate directed against the CD 33 antigen monoclonal antibody and a bacterial toxin. It was first approved antibody-toxin conjugate ever in the United States in 2000.

Ibritumomab tiuxetan is a from the monoclonal antibody ibritumomab tiuxetan and the complexing agent ( a DTPA derivative) constructed immunoconjugate is loaded immediately before his Applizierung with 90Yttrium. It is approved for the treatment of various malignant lymphomas of B- lymphocytes ( radioimmunotherapy ).

Labeled with 131Iod tositumomab, a murine monoclonal antibody, is approved for treatment of non-Hodgkin's lymphoma.

Arcitumomab is an antibody fragment ( Fab fragment ) directed against the carcinoembryonic antigen, which is expressed in particular colorectal cancer. Just before injection into the patient is loaded with Arcitumomab 99mTechnetium. With the help of SPECT can then subsequently be localized cancer or the extent of remission or possible metastasis are depicted.

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