Carolyn S. Ernst

PHASE-I CLINICAL TRIAL OF MONOCLONAL ANTIBODY IN TREATMENT OF GASTROINTESTINAL TUMOURS

A phase-I clinical trial of a murine monoclonal antibody that specifically suppresses growth of human gastrointestinal tumours in athymic mice was conducted in four patients, who were given 15-200 mg purified antibody. The monoclonal antibody persisted in the circulation for more than a week when more than 15 mg was given. Antibodies against mouse immunoglobulin developed in three of the four patients. In one patient who received autologous mononuclear cells that had been mixed with monoclonal antibody by way of a hepatic-artery catheter, hepatic metastases became smaller and their echogenic characteristics changed, and there was heavier monocyte infiltration in the histological appearance of a resected metastasis.

Efficient selection of human tumor growth-inhibiting monoclonal antibodies

A method is described for selection early after fusion for hybridomas that secrete IgG2a monoclonal antibodies (MAbs) with binding specificity for antigens on the human tumor cells used to immunize mice. By combining this preselection method with antibody-dependent macrophage-mediated cytotoxicity assays, it was possible to select those MAbs mediating a tumoricidal effect against tumor cells in culture and inhibiting the growth of tumor xenografts in nude mice. Two such MAbs, GA733 and CO441, inhibited the growth of colorectal carcinoma cells, and one of them (GA733) was effective even when administered 6 days after implantation of tumor cells. These results suggest the potential usefulness of the 2 MAbs in immunodiagnosis and immunotherapy of human tumors.

Initial clinical evaluation of two murine IgG2a monoclonal antibodies for immunotherapy of gastrointestinal carcinoma.

Eleven patients with advanced gastrointestinal (GI) carcinoma were entered in Phase I initial clinical trials with IgG2a anti-GI carcinoma monoclonal antibodies (MAbs) GA733 (five patients) or CO19–9 (six patients). Infusion of MAb GA733 in doses > 30 mg was accompanied by mild and short-lasting GI toxicity. Infused MAb GA733 was bound to each patients tumor tissue in vivo. MAb circulated in the blood for 10–25 days. All patients developed anti-mouse antibodies between 15 and 60 days post infusion. Furthermore, all but one patient raised anti-idiotypic antibodies against MAb GA733.Following administration of 10–600 mg of MAb CO19–9, no immediate or delayed toxicity symptoms were noted. Binding of infused MAb CO19–9 to tumor cells in vivo could not be detected in any of the six patients studied. The MAb circulated in the bloodstream between 5 and 12 days. Human anti-mouse antibody was detected in sera of three patients.None of the eleven patients treated with either MAb had anti-tumor responses in this Phase I clinical trial. The strong binding reactivity of MAb GA733 to tumors in vivo suggests the use of this MAb in cancer patients with less tumor burden to determine the tumoricidal efficacy of this antibody.

Production and Characterization of Monoclonal Antibodies to Peripheral and Central Nervous System Myelin

Abstract: Monoclonal antibodies against P0, myelin basic protein, or myelin‐associated glycoprotein were generated by fusing mouse myeloma cells with spleen cells from BALB/c mice immunized with central and peripheral nervous system myelin proteins. The antibodies secreted were either IgG, IgM, or IgA. Clone C6B5 (iso‐type IgM) secreted antibody(ies) that bound to both myelin basic protein and myelin‐associated glycoprotein, although binding of antibody to myelin basic protein as detected by the immunoblot technique appeared to be much less than to the myelin‐associated glycoprotein. Antibodies were characterized in solid‐phase radioimmunoassay for their species cross‐reaction, and histologically for the specificity of binding to myelin in central and peripheral nervous system tissues. These monoclonal reagents should prove valuable in studying CSF and myelin‐producing cells, since in both cases the concentration of myelin proteins is low.