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.
Frödin
J E
JE
Department of Oncology (Radiumhemmet) and Immunologic, Karolinska Hospital, Stockholm, Sweden.
Faxas
M E
ME
Hagström
B
B
Lefvert
A K
AK
Masucci
G
G
Nilsson
B
B
Steinitz
M
M
Unger
P
P
Mellstedt
H
H
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