The CD22 antigen is a 135-kDa B-lymphocyte-restricted trans-membrane glycoprotein of the immunoglobulin superfamily [1, 2]. It is a member of the sialoglycoprotein group of adhesion molecules that are involved in signal transduction and regulation of B-cell activation (mostly negative), mature B-cell homing, and the interactions of B cells, T cells and antigen-presenting cells [3–6]. The predominant CD22 isoform contains seven extra-cellular domains. CD22 is present in the cytoplasm of developing B cells, but is later expressed on the surface during B cell maturation at the time IgD expression occurs. Most circulating IgM+IgD+ cells express CD22. CD22 is strongly expressed in follicular, mantle and marginal zone B cells but is weakly present in germinal (activated or differentiating) B cells [1, 6, 7]. CD22 is not detected on other normal tissues nor is it expressed by non-lymphatic neoplastic cells. Because the expression of CD22 is lineage restricted, and, in most cases, is not lost during neoplastic transformation, it represents an attractive target for anti-lymphoma immunotherapeutic antibodies [1, 2]. Indeed, in B-cell malignancies, CD22 has been observed in over 80% of evaluated samples . Limited data, however, are available with regard to the expression of different CD22 isoforms in various lymphoma subtypes.
A key role of CD22 in B-cell function is suggested by studies showing that CD22–deficient mice have mature B cells which are more susceptible to apoptotic signals, have a shorter cellular lifespan, display a reduced number of B cells in the bone marrow, have a chronic exaggerated antibody response to antigen, and develop autoantibodies [1, 3, 9, 10]. Many of these functions could potentially be modulated by the binding of a specific anti–CD22 antibody (such as epratuzumab) and resultant internalisation and phosphorylation of CD22.
LL2, A MURINE ANTI-CD22 MONOCLONAL ANTIBODY
The humanised anti-CD22 antibody epratuzumab was developed from studies with a mouse monoclonal antibody (mLL2, originally named EPB-2) that specifically binds to the cluster C region of human CD22 . LL2 is a kappa IgG2 antibody that demonstrates high reactivity to human lymphoma tumour cells with a lack of cross-reactivity to non-lymphatic normal human tissues or tumours. In vitro immunohistochemical evaluation demonstrated reactivity of the LL2 antibody with 50 of 51 B-cell lymphoma specimens tested. The hybridoma cell line for LL2 was originally developed by Goldenberg and colleagues [1, 11], through the immunisation of BALB/c mice with Raji cell membranes (Burkitt’s lymphoma cell line) and fusion of the spleen cells of these mice with SP210 myeloma cells .
EPRATUZUMAB, HUMANISED ANTI-CD22
Epratuzumab (hLL2) is the humanised (complementarity determining region (CDR)–grafted) IgG1 kappa monoclonal antibody version of LL2 . By replacing a large proportion of the immunoglobulin sequence of murine LL2 monoclonal antibody with constituents of ...