Preclinical antitumor activity of an antibody against the leukocyte antigen CD48

Abstract

We have evaluated the antitumor activity of a murine antibody (IgG2a) against the leukocyte antigen CD48. CD48 is expressed on T and B lymphocytes, monocytes, and a wide range of lymphoid malignancies. To assess the therapeutic potential of an anti-CD48 antibody, we established a reproducible model of human B-cell (Raji) leukemia/lymphoma in C.B17/scid mice, where untreated mice develop hind leg paralysis due to tumor engraftment. Using this model, the murine anti-CD48 antibody HuLy-m3 was shown to mediate a strong in vivo antitumor effect. Long-term survival (>1 year) of scid mice was obtained after treatment with three 200-microg i.v. doses of anti-CD48 antibody on days 0, 2, and 4 after i.v. injection of tumor cells. In contrast, mice treated with an isotype control antibody developed hind leg paralysis after 34 +/- 3 days. A strong antitumor response was still observed when a dose of 20 microg of HuLy-m3 antibody was used. During preclinical investigations, we also examined a number of properties of the CD48 antigen. CD48 is present at high levels on the surface of T and B cells, but most (>95%) CD34-positive cells do not express CD48. Anti-CD48 antibodies are maintained on the surface of antigen-positive cells for extended periods (>24 h). These properties suggest that anti-CD48 antibodies may be useful in the treatment of a number of diseases including lymphoid leukemias and lymphomas.