Dual-action monoclonal antibodies have cured Hodgkin's lymphomaoutright _ in mice. The German researchers who performed the featare unsure of the mechanism that killed the tumors, but theyrecommend evaluation in human patients of their approach "to humanmalignancies that cannot be cured by standard radiation andchemotherapy."Those two types of treatment can and do cure Hodgkin's disease,which is one of the few cancers that medical science usually _ thoughnot always _ defeats.Christoph Renner and his co-authors at the Universitat des Saarlandes,in Homburg, Germany, implanted human Hodgkin's tumor cells intomice with severe combined immune deficiency (SCID). Lacking bothT- and B-cell immune defenses, these animals accepted the growingforeign graft as their own malignancy.Friday's Science. describes the Saarlanders' experiment as "Cure ofXenografted Human Tumors by Bispecific Monoclonal Antibodies andHuman T Cells."Their pair of double-barreled monoclonals _ really, bi-clonals _ eachcarried two antibody active sites. One of the bispecifics recognizedboth a Hodgkin's-associated antigen, CD30, and the main T-cell-activating antigen, CD3. The other reacted with the same target CD30,as well as a different T-cell stimulator, CD28.They constructed these two-faced antibodies from "tetradomas" byfusing two hybridoma cell lines.A day after inoculating the tumor-bearing mice with this brace ofbispecific antibodies, the Saarlanders injected them with 10 millionperipheral human blood lymphocytes. They had pre-stimulated thesecells by incubating them in vitro with tumor cells displaying the bulls'-eye CD30 antigen.Immunologist Dianne Fishwild, director of hybridoma development atGenPharm International, of Moutain View, Calif., explains: "In orderfor a T cell to kill its target tumor cell, it has to be activated, because aresting cell doesn't do anything. But even activated T cells aren't goodenough. There has to be a way to navigate them to the tumor. Andthat's how the bispecific antibodies work."Fishwild finds this Science report "interesting." She notes that "therehave been numerous other demonstrations of bispecific antibodies ofdifferent specificities, which work in similar animal models. But to myknowledge, this is the first demonstration with Hodgkin's lymphoma inmice."She sees a benefit in the way Renner et al. have structured their modelsystem to allow for in vitro preactivation of the T cells. "So you couldtake out a patient's peripheral blood," Fishwild told BioWorld Today,"activate the T cells with these bispecific antibodies, then inject bothback into the patient's body."The cells would be totally human, and also _ now being activated _should be able to recognize the tumor cells. And the bispecifics wouldhelp home in on them."

-- David N. Leff Science Editor

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