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Therapeutic Effect of Treatment with Polyclonal or Monoclonal Antibodies to -Fetoprotein That Have Been Conjugated to Daunomycin via a Dextran Bridge: Studies with an -Fetoprotein-producing Rat Hepatoma Tumor Model¹

Department of Biochemistry, School of Medicine, Hokkaido University, Sapporo, Japan [Y. T.]; Department of Microbiology, Sapporo Medical College, Sapporo, Japan [K. O.]; and Tumor Laboratory, Kokubunji, Tokyo, Japan [N. H.]

Purified monoclonal mouse or polyclonal horse antibodies (Ab) to rat -fetoprotein (AFP) were conjugated with daunomycin via a dextran bridge. The therapeutic effect of these Ab-daunomycin conjugates on an AFP-producing rat hepatoma which was inoculated s.c. in Donryu rats was studied. Tumors (s.c.) and distant metastases were present by 14 days after tumor inoculation and the serum AFP level was 35 µg/ml. The injection of the Ab-daunomycin conjugate, started on day 14, significantly prolonged host survival with inoculated controls having a median survival of 25 days compared to 57 and 60 days for the treated groups. In a second study the Ab-daunomycin conjugates were injected i.v. every other day for five times after the surgical resection of the s.c. tumor. There was a slight therapeutic effect with either antibody or daunomycin alone but treatment with the AFP Ab-daunomycin conjugates significantly prolonged survival and 60% of these treated animals were "tumor free" when sacrificed on day 100. Serial quantitation of the concentration of AFP in the serum of the treated tumor-bearing or in the tumor-resected rats correlated with the therapeutic effectiveness of the Ab-daunomycin conjugates. These experiments show that the optimal treatment with specific antibody-drug conjugates will be in hosts where there is a small residual tumor burden such as may exist following resection of a primary tumor mass. They further show that the serial quantitation of serum AFP can be utilized to determine if residual tumor is present following treatment with Ab-daunomycin conjugates.

¹ This work was supported in part by a Grant-in-Aid for Cancer Research from the Ministry of Education, Science and Culture, Japan.

² To whom requests for reprints should be addressed, at Department of Biochemistry, School of Medicine, Hokkaido University, Sapporo 060, Japan.

Received 12/ 5/86. Revised 5/ 6/87. Accepted 5/13/87.

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