CD30-specific AB1-AB2-AB3 internal image antibody network: potential use as anti-idiotype vaccine against Hodgkin's...

The tumor-associated CD30 antigen is presently under study as a target for active specific immunotherapy of Hodgkin's lymphoma with anti-idiotypic antibodies. Internal image antibodies (Ab2 beta) 9G10 and 14G9 against the CD30-specific antibody HRS-4 (Ab1) have been described, which induce a CD30-specific T- and B-cell response in BALB/c mice and New Zealand white rabbits. In extension of this work, murine monoclonal anti-idiotypic Ab2 beta 9G10, mimicking structures of the nominal CD30 antigen, was used to generate monoclonal Ab3 in mice and polyclonal Ab3 in rabbits with specificity for CD30. The Ab2 beta 9G10-specific murine monoclonal Ab3 4A4 bound specifically to the 120-kDa band of CD30 present on Hodgkin cell lines and Hodgkin tumor tissue, and effectively inhibited binding of Ab1 HRS-4 to Ab2 9G10 as well as to CD30+ cells. Monoclonal Ab3 4A4 was cytotoxic for CD30+ cell lines in vitro and effectively prevented the s.c. growth of L540 cell tumors after passive i.v. administration in a SCID mouse tumor model. While this cytotoxic effect of the IgM subclass monoclonal Ab3 4A4 was due to complement activation, the murine monoclonal Ab1 HRS-4 and a polyclonal Ab3 preparation of IgG-subclass from New Zealand white rabbits were cytotoxic by an antibody-dependent cell-mediated mechanism in vitro. In conclusion, Ab2 beta 9G10 is able to induce a CD30-specific cytotoxic IgG and IgM response. Cytotoxicity was shown to be mediated by complement activation and antibody-dependent cell-mediated cytotoxicity in vitro and in vivo and across species barriers. Thus, the CD30-like Ab2 beta 9G10 may hold promise for effective active specific immunotherapy of human Hodgkin's lymphoma.