Humoral anti-idiotypic and anti-anti-idiotypic immune response in cancer patients treated with monoclonal antibody 17-1A.
A group of 96 patients with advanced colorectal carcinoma were treated with the mouse (m) or chimeric (c) (mouse variable regions x human IgG1 constant regions) monoclonal antibody (mAb) 17-1A recognizing the tumour-associated antigen GA733-2. Eighty-two of the 83 patients treated with mmAb 17-1A and 69% of the patients given cmAb17-1A (n = 13) developed anti-idiotypic antibodies (ab2). Auto-antibodies binding to tumour cells expressing GA733-2 were found in 7% of the patients. In a further 38 patients (40%) antitumour-cell antibodies, i.e. anti-anti-idiotypic antibodies (ab3), were induced by the mAb17-1A therapy. Patients with detectable ab3 after treatment had significantly higher ab2 levels than those not developing ab3. Addition of granulocyte/macrophage-colony-stimulating factor (GM-CSF) to mmAb17-1A significantly enhanced the induction of ab2 as well as induction of anti-anti-idiotypic antibodies (ab3) compared to mmAb17-1A alone. Patients with a high increase in antitumour-cell antibodies (ab3) induced by the therapy lived significantly longer than patients with no or a low level of induction of ab3 (P = 0.016). The results indicate that induction of an idiotypic network response might be an important effector mechanism in mAb therapy.
Fagerberg
J
J
Department of Oncology, Karolinska Hospital, Stockholm, Sweden.
Ragnhammar
P
P
Liljefors
M
M
Hjelm
A L
AL
Mellstedt
H
H
Frödin
J E
JE
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000917:Antibody Formation / Q000187:drug effects; D001323:Autoantibodies / Q000096:biosynthesis; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy; D008297:Male; D051379:Mice; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000276:immunology* / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D011993:Recombinant Fusion Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor