ANTITUMOR EFFECTS OF NONCONJUGATED MURINE LYM-2 AND HUMAN-MOUSE CHIMERIC CLL-1 MONOCLONAL-ANTIBODIES AGAINST VARIOUS HUMAN LYMPHOMA CELL-LINES IN-VITRO AND IN-VIVO

Lym-2 is a murine monoclonal antibody (MoAb) directed towards a human class II molecule variant reactive with both normal and neoplastic hum an B lymphocytes. Previous studies have shown that signals transmitted by class II molecules that stimulate normal lymphocytes can be inhibi tory for B-cell lymphoma growth by signaling activation-induced cell d eath. Therefore, we sought to evaluate the effects of nonconjugated mu rine Lym-2 and a human-mouse chimeric Lym-2 (chCLL-1; with murine vari able regions and human constant regions) MoAb on the growth of various human lymphomas by using both in vitro and in vivo assays. Cell lines derived from Burkitt's lymphomas, diffuse large cell B-cell lymphomas , anaplastic large-cell lymphomas, and Epstein-Parr virus-induced B-ce ll lymphomas were incubated with Lym-2 or chCLL-1 in vitro, and effect s on proliferation were determined by [H-3]-thymidine incorporation. T he effects of Lym-2 in vitro were also compared with those of Lym-1, w hich is a similar MoAb that has been evaluated clinically. After immob ilization, which enhances crosslinking of the MoAbs, both Lym-2 and ch CLL-1 were capable of directly inhibiting the growth of various lympho ma lines in vitro. These human lymphomas were then transferred into mi ce with severe combined immunodeficiency to evaluate the efficacy of t hese MoAbs in vivo. Treatment with either murine Lym-2 or the chimeric chCLL-1 were significantly effective in improving the survival of tum or-bearing mice. These results indicate that stimulation by nonconjuga ted chCLL-1 may offer a biological approach to the treatment of variou s human lymphomas. This is a US government work. There are no restrict ions on its use.