Early detection of the CH1 murine lymphoma by tumor-associated idiotype in the serum.

In this report, we describe a sensitive C-dependent^{2 51}Cr release inhibition assay using anti-idiotype antiserum which allows early detection of the CH1 murine B-cell lymphoma by the presence of 19S tumor-associated immunoglobulin in the serum. The assay is based on the finding that sera from mice bearing the CH1 lymphoma specifically inhibit C-dependent ⁵¹Cr release from labelled CH1 cells in the presence of A-Id serum. Groups of mice were injected ip with 10², 10³, or 10⁴ CH1 cells and serum samples were collected every other day until host death. Tumor-specific idiotype was detectable as early as 8 days after a 10⁴ CH1 tumor cell challenge and by 12–14 days in mice inoculated with 10³ or 10² CH1 cells. The amount of idiotype increased in parallel with tumor burden and reached a peak titer just before host death In all cases, tumor-associated idiotype was present in the serum time significantly prior to observation of a visible tumor mass (ca. day 20–28). In subsequent experiments, mice were inoculated with 10⁴ CH1 cells and treated 16 days later with a single dose of melphalan (10 mg/kg), vincristine sulfate (0.75 mg/kg), or cyclophosphamide (100 mg/kg). Serum samples were taken from these animals and the level of serum idiotype was monitored. After M or VS drug therapy, the level of idiotype decreased in all mice, however host survival was not significantly prolonged. By contrast, mice treated with Cy survived significantly longer than untreated controls, and the serum idiotype titer in these mice decreased to undetectable levels from day 20–28. By day 37, idiotype was detectable again in the serum and all mice died of ascites tumor by day 44. The results of these experiments suggest that the presence of idiotype in the serum of a lymphoma-bearing host may provide a marker which will allow early detection of tumor growth during periods of tumor remission induced by conventional chemotherapy.