Suppression of growth of human malignant B cells by naked monoclonal antibodies that target ectoepitopes of the Igα/Igβ (CD79) component of the human B cell antigen receptor complex

4107 The disulfide linked heterodimer of Igα (mb1, CD79a) and Igβ (B29, CD79b) is noncovalently associated with the cell membrane Ig on B cells and play the pivotal role in the antigen-dependent signal transduction. Previously we reported a novel heterodimeric cell membrane antigen that was strongly expressed on some malignant B cells including prolymphocytic leukemia and non-Hodgkin’s lymphoma cells (1989, 1993). This antigen was found by use of three newly generated monoclonal antibodies (mAbs) termed SN8, SN8a and SN8b. Subsequently we determined that this antigen was the human homologue of murine Igα/Igβ (1993, 1994). These mAbs were the first proven mAbs defining ectoepitopes of Igα/Igβ. SN8 and SN8a defined ectoepitopes of Igβ (1993), whereas SN8b defined an ectoepitope of Igα (A.G. Polson et al. 2006). In the present study, we tested our hypothesis that naked (unconjugated) mAbs targeting the ectoepitopes of Igβ and/or Igα may be valuable for treating patients with B cell malignancies. SN8 showed dose-dependent growth suppression of malignant B cells while an isotype-matched control IgG and an isotype-matched control mAb SN2 showed no significant suppression. Cross-linking of the mAb and antigen using anti-mouse IgG antibodies or human CD32-transfected murine L cells enhanced the growth suppression by SN8. SN8b also suppressed growth of malignant B cells. The suppressive activities of these mAbs were further evaluated in SCID mice bearing BALL-1a B-cell tumors. A preliminary experiment suggested that SN8 and SN8b defining Igβ and Igα, respectively, synergize in suppression of the tumor growth. This conclusion was supported by the subsequent experiment. Systemic administration of SN8 improved survival of the tumor-bearing mice when the mice were followed for 180 days. SN8b was less effective than SN8. Combined use of SN8 and SN8b showed supraadditive antitumor efficacy and suggested therapeutic synergy. The results appear to support our hypothesis that naked SN8 may be useful for treating B cell malignancies and this potential will be enhanced by combined use of SN8 with SN8b.