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Tumor Regression in Monoclonal Antibody-treated Patients Correlates with the Presence of Anti-Idiotype-reactive T Lymphocytes¹

Department of Oncology (Radiumhemmet), Karolinska Hospital, S-171 76 [J. F., A-L. H., P. R., J-E. F., H. M.], and Microbiology and Tumorbiology Center, Karolinska Institute, S-171 77 [H. W.], Stockholm, Sweden

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.

¹ This work was supported by grants from the Swedish Cancer Society, the Cancer Society in Stockholm, the King Gustav V Jubilee Fund, Eva and Jerzy Cedarbaum's Foundation, and Anders Otto Swärd's Foundation.

² To whom requests for reprints should be addressed.

Received 2/24/95. Accepted 3/21/95.

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