Tumor regression in monoclonal antibody-treated patients correlates with the presence of anti-idiotype-reactive T lymphocytes.
Treatment of cancer patients with unconjugated mAbs directed against tumor-associated antigens is considered passive immunotherapy due to the main suggested effector mechanisms: antibody-dependent cellular cytotoxicity, complement-dependent cytolysis, and apoptosis. The therapeutic antibody (ab1) may, however, also give rise to an idiotypic network response, i.e., an immunizing effect. Induced anti-idiotypic antibodies (ab2) mimicking the epitope that ab1 recognizes might subsequently induce an anti-anti-idiotypic humoral (ab3) and T-cell (T3) response recognizing the nominal tumor-associated antigen. Twenty-four patients with metastatic colorectal carcinoma were treated with MAb17-1A against the tumor associated antigen GA733-2 and were analyzed for the induction of T3 cells. Five of the patients responded to mAb therapy with tumor regression. These five patients all had T cells specifically recognizing human ab2 (DNA synthesis) after treatment, while all nonresponding patients lacked such T cells. Four of the five patients with ab2-reactive T cells also showed induction of T cells recognizing GA733-2. The association between T3 cells and tumor regression was highly significant (P = 0.0005). Thus, induction of T3 cells might be an important secondary antitumor effector function of therapy with unconjugated mAbs. Antibody therapy may therefore also be considered active specific immunotherapy.
Fagerberg
J
J
Department of Oncology (Radiumhemmet), Karolinska Hospital, Stockholm, Sweden.
Hjelm
A L
AL
Ragnhammar
P
P
Frödin
J E
JE
Wigzell
H
H
Mellstedt
H
H
D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000276:immunology*; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000276:immunology; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000628:therapy*; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm