Antigen-Induced Murine B-Cell Lymphomas. III. Passive Anti-idiotype Serum Therapy and Its Combined Effect With Chemotherapy2

Abstract

The effectiveness of passive heterologous anti-idiotype (A-Id) serum therapy in combination with chemotherapy was investigated in the CH1 murine B-cell lymphoma system. Groups of B10-H-2^aH-4^bp/Wts mice were given small single doses (5–200 μl) of A-Id serum 2 days after a lethal tumor challenge of 10²–10³ CH1 cells. Most of these mice survived tumor-free for more than 80 days, whereas all control mice died within 33 days. If treatment was delayed until day 4, all mice succumbed to tumor, but some survived significantly longer than controls. Surprisingly, mice treated with a single large dose (0.5 ml) or multiple doses of A-Id serum all died of tumor as rapidly as untreated controls. A-Id-treated mice surviving the initial tumor were rechallenged with another lethal CH1 tumor inoculum. Ten of 20 rechallenged mice survived. Tumor-bearing mice were also treated with cyclophosphamide (Cy) to determine whether this agent could inhibit tumor growth. All mice given Cy (25–100 mg/kg) 4 days after they were given 2.5–10×10² CH1 cells survived indefinitely. If treatment was delayed until day 12, most mice died of tumor. However, Cy treatment increased the host survival time significantly. In contrast to the results with A-Id serum therapy, mice surviving after chemotherapy did not resist a second tumor challenge. In a subsequent experiment, A-Id serum therapy was combined with Cy drug treatment. Only 4 of 10 mice given 50 mg/kg Cy on day 11 after they received a 2.5×10² CH1 tumor challenge survived, and none of the untreated mice (0/5) or mice given A-Id serum only (0/4) on day 16 survived. By contrast, all 10 mice given 50 mg/kg Cy on day 11 and then 200 μl A-Id serum on day 16 survived throughout the observation period (>90 days).