Antitumor activity of idarubicin-monoclonal antibody conjugates in a disseminated thymic lymphoma model

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 2 x 10(6) 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 immunochemotherapeutic 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.