PRECLINICAL ANTITUMOR-ACTIVITY OF AN ANTIBODY AGAINST THE LEUKOCYTE ANTIGEN CD48

We have evaluated the antitumor activity of a murine antibody (IgG2a) against the leukocyte antigen CD48. CD48 is expressed on T and B lymph ocytes, monocytes, and a wide range of lymphoid malignancies, To asses s the therapeutic potential of an anti-CD48 antibody, me 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 tumo r engraftment, Using this model, the murine anti-CD48 antibody HuLy-m3 was shown to mediate a strong in vivo antitumor effect, Long-term sur vival (>1 year) of scid mice was obtained after treatment with three 2 00-mu g 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 s trong antitumor response was still observed when a dose of 20 mu g of HuLy-m3 antibody was used, During preclinical investigations, we also examined a number of properties of the CD48 antigen, CD48 is present a t high levels on the surface of T and B cells, but most (>95%) CD34-po sitive 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 t he treatment of a number of diseases including lymphoid leukemias and lymphomas.