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Efficacy of Tumor Cell Extracts in Immunotherapy of Murine EL-4 Leukemia

National Institute of Allergy and Infectious Diseases, Rocky Mountain Laboratory, NIH, Hamilton, Montana 59840

The ability of water-soluble tumor-associated antigens, in combination with chemotherapy, to cause regression of established EL-4 lymphocytic leukemia in C57BL/10 mice was determined. Extracts of EL-4 (G-) cells obtained by solubilization with 3 M KCI (SAE:EL-4) contained tumor-associated antigens as measured by immunodiffusion and inhibition of complement-dependent cytotoxicity using either rabbit or C57BL/10 anti-EL-4 sera.

Tumors were established by s.c. injection of 2 to 5 x 10⁴ ascites-grown EL-4 tumor cells. Twenty-five- or 100-µg quantities of mitomycin C were administered by intralesional injection 7 days after implantation when the tumors were about 4 mm in diameter. Intralesional injection 2 days later of oil-in-water emulsions containing 150 or 300 µg SAE:EL-4 caused complete regression of tumors in 50 to 80% (p < 0.01 to < 0.001) of treated animals. Administration of 25 or 100 µg mitomycin C without immunotherapy cured 14 of 70 (20%) and 16 of 60 (27%) of treated animals, respectively. Conversely, oil emulsions of SAE:EL-4 when tested without chemotherapy were ineffective. Essentially without value (less than 20% cures) were treatments which included chemotherapy followed by immunotherapy with emulsions containing 3 M KCI extracts of C57BL/10 spleen cells, L1210 tumor cells, or SAE:EL-4 without being incorporated into oil droplets but merely dissolved in phosphate-buffered saline (0.15 M NaCl and 0.01 M NaH₂PO₄-NaHPO₄, pH 7.3). Animals cured with combination therapy rejected a retransplant of EL-4 cells but not a transplant of B-16 tumor cells. High cytotoxic activity against EL-4 cells was detected in the sera from mice cured with either chemotherapy or chemoimmunotherapy. All of these findings demonstrate that it is possible to isolate tumor-associated antigens that act as immunostimulants and possess, when emulsified in oil droplets and combined with intratumor chemotherapy, high tumor regressive activity.

¹ To whom requests for reprints should be addressed.

Received 3/20/78. Accepted 12/20/78.