Induction of anti-idiotypic (ab2) and anti-anti-idiotypic (ab3) antibodies in patients treated with the mouse monoclonal antibody 17-1A (ab1). Relation to the clinical outcome--an important antitumoral effector function?
Forty-three patients with metastatic colorectal carcinoma (CRC) were treated with the unconjugated mouse monoclonal antibody (MAb) 17-1A (ab1) only. The presence of antiidiotypic antibodies (ab2) and anti-antiidiotypic antibodies (ab3) were analyzed using an ELISA technique and a mixed hemadsorption assay respectively. Ninety-five percent (41/43) of the patients developed ab2 both of the IgM and the IgG classes. Forty-seven percent (20/43) of the patients had detectable ab3 after therapy, two of them also before administration of MAb 17-1A. Binding in vitro of ab3 (ab1) to CRC cells could be specifically inhibited by ab1. Ab3 bound to human monoclonal antiidiotypic antibodies and to a goat antiidiotypic antibody (ab2). Both these ab2 were directed against MAb 17-1A (ab1). There was a strong correlation between the presence of ab3 and the clinical outcome. Ab3+ patients survived significantly longer than those who did not develop ab3 antibodies, 80 weeks vs 38 weeks (p less than 0.001). A statistically significant correlation was found between the presence of ab3 and the anti-tumor response (CR + PR + MR + SD) (p = 0.01). Thus, induction of an antiidiotypic cascade seems to be an important antitumor effector function of MAb in the treatment of cancer patients.
Department of Oncology (Radiumhemmet) and Immunologic, Karolinska Hospital, Stockholm, Sweden.
J E
JE
Frödin
M E
ME
Faxas
B
B
Hagström
A K
AK
Lefvert
G
G
Masucci
B
B
Nilsson
M
M
Steinitz
P
P
Unger
H
H
Mellstedt
D000888:Antibodies, Anti-Idiotypic / Q000032:analysis / Q000096:biosynthesis*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D000917:Antibody Formation; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002277:Carcinoma / Q000276:immunology* / Q000401:mortality / Q000628:therapy; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000401:mortality / Q000628:therapy; D003131:Combined Modality Therapy; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006382:Hemadsorption; D006801:Humans; D008297:Male; D012074:Remission Induction; D012397:Rosette Formation; D016019:Survival Analysis
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal