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 t umor-associated antigens is considered passive immunotherapy due to th e main suggested effector mechanisms: antibody-dependent cellular cyto toxicity, complement-dependent cytolysis, and apoptosis, The therapeut ic antibody (ab(1)) may, however, also give rise to an idiotypic netwo rk response, i.e., an immunizing effect, Induced anti-idiotypic antibo dies (ab(2)) mimicking the epitope that ab(1) recognizes might subsequ ently induce an anti-anti-idiotypic humoral (ab(3)) and T-cell (T-3) r esponse 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 T-3 cells, Five of the patients responded to mAb ther apy with tumor regression. These five patients all had T cells specifi cally recognizing human ab(2) (DNA synthesis) after treatment, while a ll nonresponding patients lacked such T cells. Four of the five patien ts with ab(2)-reactive T cells also showed induction of T cells recogn izing GA733-2. The association between T-3 cells and tumor regression was highly significant (P = 0.0005). Thus, induction of T-3 cells migh t be an important secondary antitumor effector function of therapy wit h unconjugated mAbs. Antibody therapy may therefore also be considered active specific immunotherapy.