This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Smyth, M. J. Articles by Pietersz, G. A. Search for Related Content PubMed PubMed Citation Articles by Smyth, M. J. Articles by Pietersz, G. A.

Antitumor Activity of Idarubicin-Monoclonal Antibody Conjugates in a Disseminated Thymic Lymphoma Model¹

Research Centre for Cancer and Transplantation, Department of Pathology, University of Melbourne, Parkville, 3052 Victoria, Australia

Many of the experimental approaches used in the search for new targeted drug delivery systems ignore the disseminated nature of metastatic disease; the development of more relevant tumor models is therefore a priority. A reproducible and tumor-specific model has been generated by inoculating (C57BL/6 x BALB/c) F₁ (Ly-2.2⁺) mice i.v. with the Ly-2.1⁺ murine ITT(1) 75NS E3 thymic lymphoma (E3). At a dose of 2x10⁶ cells, E3 tumors grew in a disseminated fashion, arising initially and predominantly in the lung and kidney, and later and less often in the thymus, spleen, and other tissues. In addition, histopathological examination and flow cytometry of blood did not detect E3 tumor cells in most other organs or in the circulation throughout the course of disease. The mean survival time (MST) of untreated mice was both reproducible and proportional to the number of E3 tumor cells injected and was therefore used to demonstrate the suitability of this model for immunochemother-apeutic studies. When examining the antitumor efficacy of idarubicin-monoclonal antibody conjugates, it was observed that the survival times of treated mice were consistent within groups and between experiments. The disseminated E3 (Ly-2.1⁺) tumor model, like the s.c. E3 tumor model, demonstrated the dose-dependent efficacy of idarubicin-anti-Ly-2.1 conjugate treatment and illustrated both the negligible antitumor activity and toxicity of idarubicin alone. Furthermore, lung and kidney weight measurements formally demonstrated that the increased MST of treated mice represented a reduction of E3 tumor burden in these organs. This model provides a useful tool for study of the immunochemotherapy of disseminated tumors in mice and further illustrates the antitumor activity of idarubicin-monoclonal antibody conjugates.

¹ This work was supported by Farmitalia Carlo Erba, Milan, Italy.

Received 12/29/88. Accepted 10/22/90.