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Microbiology and Pharmacology Laboratory, Indian Institute of Science, Bangalore 12, India
The biological activity of rabbit anti-Yoshida ascites sarcoma (YAS) sera was studied. Immune antisera exhibited cytotoxic effects at a 1:100 dilution on YAS cells in vitro, causing vacuolation and disruption of the cytoplasm accompanied by karyolysis. Rabbit antisera, given i.p. in gradually increasing daily doses over a period of 8 days, completely inhibited the growth of YAS in isogenic Wistar rats (A/IISc) and, after absorption with liver and spleen of the A/IISc Wistar rats, the animals still showed tumor suppression. Anti-rat liver and anti-rat spleen sera from rabbits could prolong the survival period of rats with YAS but were unable to inhibit tumor growth. These findings suggest the existence of tumor-specific antigens as well as the presence of normal tissue antigens in the tumor.
After tumor inhibition, the rats exhibited lasting immunity as evidenced by rejection of lethal doses after subsequent tumor transplantation. Electrophoresis of the sera of these rats showed considerable increase in the
-globulin fraction. Agglutinating antibodies in the sera were detected by a passive hemagglutination test. With trypan blue dye exclusion techniques, the presence of heat-stable (for 30 min at 56°) and complement-dependent cytotoxic antibodies to YAS cells could be shown in immune rat sera. The cytotoxic effect was observed, but with a reduced titer, even after thorough absorption of the immune sera with rat spleen and lymphoid cells. The neutralizing effect of immune rat sera on YAS cells was shown by the inability of lethal doses of YAS cells (10 million) to induce tumors in rats after incubation with immune rat sera. At twice this dose of YAS cells (20 million), only 40% of the injected rats developed tumors; they died after a prolonged survival period of 20 days while controls survived for 10 days.
The heterologous antisera, although not specific, can still be a useful therapeutic measure for some tumors, and the lasting immunity conferred is likely to play a significant role in control of growth and metastatic dissemination of the tumor cells.
Received 11/12/69. Accepted 4/14/71.
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