Bispecific antibody-mediated destruction of Hodgkin's lymphoma cells

CD30 is a molecule that is overexpressed on the surface of Hodgkin's lympho ma cells. Therefore, CD30 represents a potential candidate for immunotherap y. In this study, we report the in vitro results of two bispecific molecule s (BSMs) that target CD30 to trigger molecules expressed on myeloid effecto r cells. The first BSM is composed of the Fab' fragment of a CD30-specific antibody, Ki-4, chemically linked to the Fab' fragment of the humanized CD6 4 (Fc gamma RI)-specific antibody, H22 (H22XKi-4). In the second BSM, the H 22 Fab' is replaced with the Fab' fragment of the CD89 (Fc alphaR)-specific , antibody, A77 (A77XKi-4). Both BSMs were able to bind specifically to lym phoma cell lines expressing CD30. In addition, the H22XKi-4 and A77XKi-4 BS Ms were shown to bind cells expressing CD64 and CD89, respectively. Both BS Ms mediated potent, dose-dependent antibody dependent cell-mediated cytotox icity (ADCC) of CD30-expressing tumor cell Lines when human monocytes were used as effector cells. In addition, freshly prepared polymorphonuclear leu kocytes (PMNs) and effector cells in whole blood were able to mediate the A DCC of targets in conjunction with the A77XKi-4 BSM in some, but not all, e xperiments. Furthermore, we examined the ability of monocyte-derived macrop hages (MDMs) to phagocytose CD30-expressing tumor cell lines in conjunction with the BSM. MDM-mediated phagocytosis was significantly enhanced in the presence of both BSMs. These results demonstrate that targeting lymphoma ce lls via CD30 to the myeloid high affinity Fc receptor for IgG and to the Fc receptor for IgA results in potent in vitro anti-tumor activity. (C) 2001 Elsevier Science B.V; Ail rights reserved.