Host-mediated Antibody-dependent Cellular Cytotoxicity Contributes to the in Vivo Therapeutic Efficacy of an Anti-CD7-Saporin Immunotoxin in a Severe Combined Inuminodefficient Mouse Model of Human T-Cell Acute Lymphoblastic Leukemia1

We have investigated the anti-leukemia effect that is exerted by the murine anti-CD? antibody HB2 in a severe combined immunodeflcient (SCID) mouse model of human T-cell acute lymphoblastic leukemia (T-ALL) and determined the contribution that this antibody effect makes to the therapeutic potency of a saporin immunotoxin (IT) constructed with the same antibody. The anti-leukemia effect is not exerted through com plement-mediated lysis or through direct growth-inhibitory signaling af ter binding of antibody to the CD7 molecule on the T-ALL cell surface but rather through antibody-dependent cellular cytotoxicity (ADCC). Thus, the in vivo depletion of SCID mice of their natural killer cells almost completely abolishes the therapeutic effect of native HB2 anti-CD7 anti body and moreover significantly reduces the in vivo therapeutic perform ance of the anti-CD? HB2-SAPORIN IT. Furthermore, an IT constructed with the F(ab')2 fragment of the same anti-CD? antibody (HB2-F(ab')2SAPORIN), which is incapable of recruiting natural killer cells, per formed significantly less well therapeutically than HB2-SAPORIN IT. There was also a significant improvement in the therapeutic performance of the HB2-F(ab')rSAPORIN IT in SCID-HSB-2 mice when used in combination with intact HB2 antibody, presumably through restoration of an ADCC attack on the target HSB-2 cell. These combined data indicate that ADCC in the SCID mouse does contribute additively together with toxin to the in vivo therapeutic potency of the HB2-SAPORIN IT directed against this human T-ALL cell line and that this has potentially important implications for the utility of this and other related classes of ¡mmunotherapeutic in human therapy.