Serotherapy of L1210 murine leukaemia—reasons for ineffectiveness of in vivo treatment by L.1 monoclonal antibody

Abstract

Summary A monoclonal antibody (L.1), reacting in vitro specifically with L1210 leukaemia cells in a complement-dependent cyctotoxicity assay (CDC), has been exploited for serotherapy studies. Different regimens of L.1 treatment of CD2F1 mice bearing the semi-syngeneic L1210 leukaemia did not prolong the life span of tumor-bearing animals. Moreover, the administration of L.1 did not enhance the antitumour effects of cyclophosphamide. Studies of in vivo localization showed that L.1 was able to bind specifically to L1210 leukaemic cells, although 30-40% of the cells remained negative. The presence of L.1 in mouse blood was demonstrated up to 15 days after the inoculation. On the other hand, in vivo administration of L.1 was probably accompanied by loss of the cytotoxic activity, perhaps through a mechanism of complement inactivation, since the presence of undiluted normal mouse serum in a CDC assay inhibited the cytotoxic activity of L.1. Moreover, serum from L.1-treated mice did not display any cytotoxic activity, although the presence of the antibody could be demonstrated by indirect immunofluorescence.Shedding of the antigen defined by L.1 was probably not responsible for the failure of the serotherapy, since the L. 1 neutralizing antigen could be found in body fluids only long after the start of therapy.

Combined therapy with anti-p-glycoprotein antibody and macrophage colony-stimulating factor gene transduction for multiorgan metastases of multidrug-resistant human small cell lung cancer in nk cell-depleted scid mice

“…The mechanism of therapeutic effects of MRK‐16 and MH162 in vivo remains unknown (Beck, 1995). Complement‐dependent cell lysis and ADCC reactions are known to be important in Ab‐dependent cancer cell killing in vivo (Hamada and Tsuruo, 1986; Heike et al, 1991; Tsuruo et al, 1989; Sone et al, 1996; Nishioka et al, 1997; Testorelli et al, 1983; Mayer et al, 1994). However, none of the anti‐P‐gp Abs tested induced complement‐dependent cell lysis by serum of SCID mice against H69/VP cells in an 8‐hr 51 Cr‐release assay (data not shown).…”