Disease relevance of CD52

• Alemtuzumab is a humanized monoclonal antibody to CD52 and has activity in chronic lymphocytic leukemia [1].
• CD52 is a phosphatidylinositolglycan (PIG)-anchored glycoprotein (PIG-AP) expressed on normal T and B lymphocytes, monocytes, and the majority of B-cell non-Hodgkin lymphomas [2].
• The other patient who was initially CD52-positive, became CD52-negative after 6 weeks of treatment, and developed progressive symptoms of T cell prolymphocytic leukemia [3].
• In contrast, in chronic lymphocytic leukemia, CD52 antibodies may be more effective in the setting of minimal residual disease and may allow harvesting of uncontaminated stem cells [4].
• The aim of our study was to evaluate CD52 as a target molecule for antibody therapy for multiple myeloma [5].

High impact information on CD52

• The administration of the immunosuppressive humanized monoclonal antibody CAMPATH 1-H, which recognizes CD52 on lymphocytes and monocytes, is associated with a first-dose cytokine-release syndrome involving TNFalpha, IFNgamma, and IL-6 clinically [6].
• The hamster cell line HE5 has been derived from primary hamster embryo cells by transformation with human adenovirus type 2 (Ad2) [7].
• The unoccupied cellular DNA sequence in cell line HE5 , corresponding to the site of the junction between Ad2 and hamster cell DNA, was also cloned; 120-130 nucleotides in the cellular DNA were found to be identical to the cellular DNA sequence in the cloned junction DNA fragment, up to the site of the junction [7].
• Campath-1H is a humanized monoclonal antibody that reacts with the CD52 antigen present on human lymphoid and myeloid cells [8].
• Two stable sublines of MDA-MB-231 cells (HC1 and HE5) expressing functional estrogen receptors were studied for their ability to grow and invade in vitro and to metastasize in athymic nude mice [9].

Chemical compound and disease context of CD52

• EXPERIMENTAL DESIGN: We evaluated 294 hematologic neoplasms for the presence of CD52 using standard immunohistochemical techniques on paraffin-embedded biopsy specimens fixed with formalin, B-Plus, Zenker's acetic acid, or B5-formalin [10].
• N-linked glycan of a sperm CD52 glycoform associated with human infertility [11].
• We investigated engraftment, acute GVHD incidence and severity, and pharmacokinetics of alemtuzumab associated with the use of low-dose alemtuzumab/cyclophosphamide/total body irradiation and ASCT for patients with aggressive CD52-positive hematologic malignancies [12].
• We describe a patient with T-PLL/SCL, who atypically presented with severe seropositive polyarthritis and skin lesions, responding to treatment with human CD52 antibody, CAMPATH-1H and pentostatin [13].
• Alemtuzumab targets the more ubiquitously expressed CD52 antigen and is therefore associated with a higher frequency of toxicity, particularly immunosuppression, but has appreciable activity in fludarabine refractory CLL [14].

Biological context of CD52

• This change in phenotype from CD52-positive to -negative during CAMPATH-1H therapy points out a need to develop strategies for maintaining antigenic expression during monoclonal antibody therapy [3].
• The activation of CD4+ T cells by anti-CD52 antibodies was inhibited by cyclosporin A, suggesting a role for the calcineurin-dependent signal transduction pathways [15].
• The relationship between this differential insertion and differences in glycosylation of rat and human CD52 is discussed [16].
• Cloning of the CD52 from a B-lymphocyte tumour cDNA library revealed two closely related sequences differing only at two amino acids C-terminal to the proposed point of glycosylphosphatidylinositol (GPI)-linkage [17].
• The peptide backbone of CD52, consisting of only 12 aminoacids, is generally considered no more than a scaffold for post-translational modifications, such as GPI-anchor and especially N-glycosylation which occur at the third asparagine [16].

Anatomical context of CD52

• In either event, detection of affected T cells, especially CD52-negative T cells, may be useful for the evaluation of long-term clinical remission in PNH [18].
• In summary, this study shows that the GPI-anchored antigen CD52 is not only a useful marker to distinguish eosinophils from neutrophils [19].
• We examined the CD52 expression on CD45+ and CD45- plasma cell populations to evaluate the potential for using alemtuzumab for these disorders [1].
• A series of rat and genetically reshaped human CD52 antibodies has been assessed for the ability to deplete lymphocytes in vivo to induce immunosuppression and for the treatment of lymphoid malignancies [4].
• CD52 is a 21- to 28-kd nonmodulating cell surface glycosylphosphatidylinositol-linked glycoprotein that is abundantly expressed (up to 5 x 10(5) molecules per cell) on most normal and malignant lymphocytes and monocytes [4].

Associations of CD52 with chemical compounds

• Whereas the phorbolester phorbol myristate acetate was able to downregulate the expression of CD52 on eosinophils in a dose-dependent manner, different eosinophil activating cytokines and chemotaxins had no effect [19].
• The results showed that the single CD52 N-glycosylation site is occupied by large sialylated, polylactosamine-containing, core-fucosylated tetraantennary oligosaccharides [20].
• The CAMPATH-1 (CD52) antigen is a 21-28 kDa glycopeptide which is highly expressed on lymphocytes and macrophages and is coupled to the membrane by a glycosylphosphatidylinositol (GPI) anchoring structure [15].
• From the results of both in vivo and in vitro studies it was concluded that androgen and temperature are principal factors synergistically modulating epididymal CD52 expression [21].
• Novel targeted therapies using monoclonal antibodies against receptors, including CD2, CD52, the beta subunit of the interleukin-2 receptor, and small molecules such as tipifarnib, are undergoing evaluation in clinical trials [22].

Regulatory relationships of CD52

• Both CD4+ CD45RA and CD4+ CD45RO T cells were stimulated to proliferate by anti-CD52 antibodies in the presence of appropriate co-stimulatory factors [15].
• In the presence of phorbol esters and cross-linking anti-Ig antibodies, mAbs specific for CD52 induced proliferation and lymphokine production in highly purified resting CD4+ and CD8+ T lymphocytes [15].

Other interactions of CD52

• In addition to the absence of CD52, the PIG-AP CD48 and CD59 were not detectable on the CD52- T cells in 2 patients [2].
• Binding of rATG to individual myeloma cell-surface proteins, primarily CD38, CD52, CD126, and CD138, was demonstrated by competitive inhibition experiments with targeted monoclonal antibodies [23].
• Anti-CD52 antibodies also augmented the anti-CD3 mediated proliferative response of CD4+ and CD8+ T cells when the two antibodies were co-immobilized onto the same surface or cross-linked in solution by the same second antibody [15].
• The neoplastic cells, in all cases, expressed monoclonal immunoglobulin light chain (k, 55; l, 20) and CD19, and every case assessed was positive for CD20 (n=68) and CD52 (n=60) [24].
• The HE5 mRNA, which was recently shown to encode the peptide backbone of the human leukocyte differentiation antigen CDw52, showed maximum levels in the distal corpus epididymidis and in the vas deferens, whereas the HE2 mRNA was found predominantly in the caput and proximal corpus sections of the epididymis [25].

Analytical, diagnostic and therapeutic context of CD52

• In addition, reverse transcription-polymerase chain reaction and Northern blot analysis showed that CD52 mRNA was constitutively expressed in eosinophils but not in neutrophils [19].
• The humanized CAMPATH-1H antibody, which is directed against CD52, is very efficient at mediating lymphocyte depletion in vivo, and is currently being used in clinical trials for lymphoid malignancy and rheumatoid arthritis [15].
• CD52 antibodies provide effective therapy for chronic leukemias, such as T-cell prolymphocytic leukemia and some subtypes of B-cell chronic lymphocytic leukemia, that may be resistant to conventional chemotherapy [4].
• The possible implications for the function of CD52 and serotherapy with anti-CD52 antibodies are discussed [17].
• CD52 is not a promising immunotherapy target for most patients with multiple myeloma [5].

References