1. Field of the Invention
The invention relates to a monoclonal antibody specifically directed against CD164.
2. Related Prior Art
Such antibodies are known from DE 195 30 272 C1 and DE 195 30 273.
CD164 is a glycosylated cell surface protein that originally has been identified as peanut agglutinin-(PNA)-binding glycoprotein.
Malignant cells of a number of human tumors have peanut agglutinin(PNA)-binding glycoproteins on their cell surface. These PNA-binding glycoproteins offer inter alia the possibility of bringing detection agents and/or therapeutically effective agents directly onto the corresponding cells and of binding these to them. The glycoproteins MUC1, MUC2 and MUC3, named according to the MUC nomenclature which has in the meantime been introduced, have been known for a number of years. A recently identified cell surface glycoprotein is the protein MGC-24, whose amino acid sequence and corresponding nucleotide sequence have been fully identified by Masuzawa et. al., J. BIOCHEM. 112, 609-615 (1992).
Recently, a variant or isoform of the protein MGC-24 has been found, designated MGC-24v. MGC-24 and MGC-24v are almost completely identical in their extracellular domains. However, MGC-24 is a predominantly secreted protein whereas MGC-24v is a type I integral membrane protein. With its molecular weight of 160 kDa MGC-24v is a homodimer of two 80 kDa subunits.
In a CD classification the glycoprotein MGC-24v was designated CD164, which designation will be used hereinafter.
The function of CD164 is still completely unknown. However, this cell surface protein is being expressed by a variety of neoplastic epithelial tissues. Therefore, it is ideally suited as a target point for a specific cellular diagnosis and therapy of such tumors.
Especially in antibody specifically binding to CD164 could be a mediator for a corresponding targeted diagnostic or therapeutic agent.
Such an antibody can be linked to both simple detection agents such as fluorescent dyes or radioactive materials as well as special, therapeutically-effective agents.
DE 195 30 272 C1 discloses a monoclonal antibody binding to MGC-24 and being designated 103B2. A further antibody against MGC-24 is disclosed in DE 195 30 273 C1. This antibody is designated 105A5. In the meantime it has turned out that both antibodies also identify the isoform MGC-24v, i.e. CD164 (Zannettino et al., "CD164 Workshop Panel Report", in: Leucocyte Typing VI, Kishimoto, T., et al., Garland Publishing, New York (in press)).
For detecting and targeted influencing the antigen it is desired to have different monoclonal antibodies available so that results can experimentally be verified with high probability.
Further, different monoclonal antibodies directed against the same antigen can differ with respect to their sensitivities and cross reactivities. In case several monoclonal antibodies against a given antigen are available, the antibody suited best can be chosen depending from the application.
Antibody 103B2, disclosed in DE 195 30 272 C1 is of immunoglobulin class IgG3 whereas antibody 105A5, disclosed in DE 195 30 273 C1 is of immunoglobulin class IgGM.
Antibodies, i.e. immunoglobulins, are comprised of variable regions having the function of specific epitope recognition, as well as of constant regions being characteristic for a immunoglobulin class. The constant regions of the antibodies have a substantial influence on their characteristics, too. Antibodies of immunoglobulin class IgM form tetrameric structures whereas antibodies of IgG class are monomeric. Further, there are four different subclasses of immunoglobulin class IgG which differ with respect to their disulfide bridge binding, their stability and further physiochemical properties.
The heterogeneity of the constant regions of the immunoglobulins is being used above all with the today usual indirect detection methods wherein antibodies are detected by secondary antibodies linked to detecting agents. These secondary antibodies bind specifically to the constant regions of the primary antibodies binding to the antigens. Secondary antibodies in most cases detect thus only one immunoglobulin class.