CD22 as a target of passive immunotherapy.
CD22 is a 135-kd B-cell restricted sialoglycoprotein present in the cytoplasm of virtually all B-lineage cells but expressed on the B-cell surface only at mature stages of differentiation. In humans, the vast majority of IgM(+)IgD(+) B cells express cell-surface CD22, while in lymphoid tissues CD22 expression is high in follicular mantle and marginal zone B cells and weak in germinal center B cells. In B-cell malignancies, CD22 expression ranges from 60% to 80% depending on the histological type and on the assays used. The function of the CD22 molecule is uncertain, although recent studies have suggested roles for the molecule both as a component of the B-cell activation complex and as an adhesion molecule. CD22-deficient mice have a reduced number of mature B cells in the bone marrow and circulation; the B cells have a shorter lifespan and enhanced apoptosis, thus indicating a key role of this antigen in B-cell development/survival. After binding with its natural ligand(s) or antibodies, CD22 is rapidly internalized; this provides a potent costimulatory signal in primary B-cell and proapoptotic signals in neoplastic B cells. Preclinically CD22 has been shown to be an effective target for immunotherapy of B-cell malignancies using either "naked" or toxin-labeled or radiolabeled monoclonal antibodies. Clinical trials in patients with non-Hodgkin's lymphoma (NHL) (both indolent and aggressive disease) are now ongoing with a humanized naked anti-CD22 antibody (epratuzumab, Amgen Inc, thousand Oaks, CA and Immunomedics Inc, Morris Plains, NJ) used as single agent or in combination with other monclonal antibodies (ie, rituximab) and/or chemotherapy. Preliminary data from these studies showed these approaches to be effective and well-tolerated.
Amgen Inc, Thousand Oaks, CA 91320, USA.
Alessandra
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Cesano
Urte
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Gayko
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015815:Cell Adhesion Molecules; D006801:Humans; D007116:Immunization, Passive; D037102:Lectins; D016393:Lymphoma, B-Cell / Q000188:drug therapy; D011947:Receptors, Antigen, B-Cell; D051918:Sialic Acid Binding Ig-like Lectin 2
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000970:Antineoplastic Agents; C497867:CD22 protein, human; D015815:Cell Adhesion Molecules; D037102:Lectins; D011947:Receptors, Antigen, B-Cell; D051918:Sialic Acid Binding Ig-like Lectin 2; C448700:epratuzumab