The objective of the present study was to establish a model system for the evaluation of passive immunotherapy of murine
leukemias.
Monoclonal antibodies directed at
T lymphocyte differentiation antigens (Thy 1 and Lyt 2) were tested for their effect on
tumors that were grown in hosts congenic for the target
antigen.
Tumor challenges were selected that were at least 500 times the dose that was lethal in 50% of untreated controls. The A strain
leukemia, ASL.1, was transplanted subcutaneously into a/Thy 1.1 congenic hosts. Intraperitoneal administration of anti-Thy 1.2
monoclonal antibodies of the
IgG3 and
IgM classes reduced
tumor growth. Up to 90% of the mice receiving antibody of the
IgG3 subclass failed to develop
tumors, whereas
IgM antibodies prolonged survival time, but the mice eventually died of
tumors. Antibody was most effective if administered within 24 hr of
tumor inoculation; delay of antibody injection for 48 hr prolonged host survival but did not eradicate cells at the injection site or prevent
metastases. The C57BL/6-derived
tumors, ERLD and EL4, were evaluated for susceptibility to treatment with antibody directed at the Lyt 2.2
alloantigen using the protocol that was effective in treating aSL.1.
Monoclonal antibody of the
IgG2a subclass was effective in the case of C57BL/6/Lyt 2.1 congenic mice bearing ERLD, but caused a decrease in survival time of mice bearing the transplanted EL4
tumor. Thus, antibody of the appropriate
immunoglobulin subclass can be effective in controlling
tumor growth if administered in the optimal treatment regimen, but inherent features of the
tumor cell ultimately determine whether abrogation or enhancement of growth will occur.