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 antiGI carcinoma monoclonal antibodies (MAbs) GA733 (five patients) or CO19-9 (six patients). Infusion of MAb GA733 in doses greater than 30 mg was accompanied by mild and short-lasting GI toxicity. Infused MAb GA733 was bound to each patient's 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.
Herlyn
D
D
Wistar Institute of Anatomy and Biology, Philadelphia, PA.
Sears
H F
HF
Ernst
C S
CS
Iliopoulos
D
D
Steplewski
Z
Z
Koprowski
H
H
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000032:analysis; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000032:analysis; D002272:Carcinoembryonic Antigen / Q000032:analysis; D003110:Colonic Neoplasms / Q000276:immunology / Q000628:therapy*; D004341:Drug Evaluation; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007136:Immunoglobulins / Q000032:analysis; D007167:Immunotherapy / Q000009:adverse effects; D051379:Mice; D012004:Rectal Neoplasms / Q000276:immunology / Q000628:therapy*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate; D002272:Carcinoembryonic Antigen; D007074:Immunoglobulin G; D007136:Immunoglobulins