Interleukin 2 enhances the efficiency of immunotoxins in the treatment of mice with ascitic tumors.

Two multivalent immunotoxins (ITs) with cytotoxic potential against Thy 1.2-expressing tumor cells were used in association with mouse interleukin 2 (IL2) for treatment of mice bearing ascitic EL4 lymphomas. The combined treatment, ITs + IL2, induced an enhanced antitumor effect revealed by a significant prolongation of the survival time of mice as compared to the simple treatment with ITs or IL2 alone. According to the survival of mice treated by combined therapy, the proportion of killed tumor cells rose up to 94% as resulted from the dose-dependent curve of the survival of nontreated mice versus the number of tumor cells inoculated.

Antitumor effect of sublethal irradiation caused by its tolerance abrogating capacity.

After the resection of methylcholanthrene-induced fibrosarcomas, representing 1--2% of total body weight, "R" rats were immunized with glutaraldehyde-fixed tumor cells, irradiated sublethally [0.1419 C kg-1 (550 R)], and restored immunologically by thymus, spleen and bone marrow cells. Afterwards, 87.5% of them were able to reject a viable challenge cell graft of 1 X 10(5) cells. Sublethal irradiation alone had the same effect, reflected by 90% of rats rejecting the grafts. Five control lots were run. They showed that none of the treatments, applied to "tumor-resected" animals could provide normal animals with the same defense capacity. Results point to the decisive role of the transient presence of the tumor in the host and of the sublethal irradiation in restoration of its defense capacity. Role of partial tolerance, in producing the host's immune inhibition, and of the capacity of irradiation to abrogating it, are discussed.

Some data concerning immune processes in concomitant tumor immunity experimental models. Comparative in vivo and in vitro investigation I. In vivo experiments.

Concomitant tumor immunity evinced by C57BL/6 mice, bearing a MC-induced sarcoma, was evaluated by graded challenge doses for different primary tumor sizes (2-3,4-6,8-12% tumor weight of the total body weight TW/TBW). 100% of mice bearing tumors, representing 2--6% of total body weight, rejected doses from 0.2--1 X 10(4) cells. The gradual curtailment of the concomitant tumor immunity, depending on increasing TW/TBW ratio, could be evaluated, using adequately increasing challenge doses. The immune equipotency of the whole s.c. body area, the failure to modify the concomitant tumor immunity by drainin node excision and the demonstration of its dependency upon the total challenge-dose and its independency upon fractionated multilocular inoculation of the challenge, showed clearly that the concomitant tumor immunity is a local expression of general immunity. The experimental model allows a valuable biological assessment of the tumor-beareer immune status and represents likewise an adequate tool for immunotherapeutic effects estimation.

Some data concerning immune processes in concomitant tumor immunity experimental models. Comparative in vivo and in vitro investigations II. In vitro experiments.

The humoral and cellular immune status of C57BL/6 male mice and "R" male rats bearing MC-induced sarcomas were investigated in vitro, using 51Cr-releasing and mixed hemadsorption assays. Analysis was performed on mice subjected to concomitant tumor immunity (CTI) model experiments or bearing primary tumors of different sizes, that was done also in rats. Chromatographic fractions, assumed to contain tumor specific antigens, antibodies or antigen-antibody complexes were identified by their absorption capacity upon specially prepared syngeneic immune sera. Free antibody and antigen-antibody complexes, accompanied with a weak cell mediated immunity (CMI) were correlated with efficient CTI in 2--3% TW/TBW tumor bearers. Homoral immunity (HI) showed sometimes an important increase after challenge administration. High levels of free antigen and antigen-antibody complexes, lack of antibodies and CMI were correlated with CTI absence in huge tumor bearers, representing 30--37% of total body weight. Conditions determining variability of results reported by different authors and the possible mechanisms by which serum immune factor may impair the tumor bearer's immune status are discussed.