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Immunological Stimulation with Modified Lymphoma Cells in a Minimally Responsive Tumor-Host System¹

Departments of Surgery [M. D. P., F. S. B., R. J. R., C. M. L., J. M. M.] and Biochemistry [M. D. P.], The University of Texas Southwestern Medical School, Dallas, Texas 75235

The P1798 lymphoma-BALB/c mouse system is one characterized by minimal immunological response during progressive tumor growth. No antitumor antibody could be demonstrated either coating P1798 cells or free in the serum of tumor-bearing mice. Ten P1798 cells constituted a lethal dose to 75% of the animals, but survivors were subsequently able to reject 100 and then 500 cells, suggestive of a limited immune response. A standard 3-dose vaccination regimen with modified P1798 cells was unsuccessful in protecting the host against subsequent challenge with viable tumor cells. Modifying reagents were selected to react with sulfhydryl groups and carbohydrate structures, to decrease negative charge, and to involve combinations of these. Using an allogeneic antiserum absorbed with normal BALB/c tissues, presence of a P1798 membrane antigen not present in normal lymphoid cells was established. Demonstration of this antigen prompted long-term immunization experiments with P1798 cells treated with iodoacetamide or Mitomycin C. Up to 94% of mice given 12 to 13 vaccinations over a period of 4 to 5 months rejected 10³ viable P1798 cells. Most of these animals were resistant when rechallenged later with 10⁴ cells. Correlating with development of resistance was the appearance of antibody in the hyperimmunized BALB/c mice. This antibody and that in absorbed allogeneic antiserum were demonstrable by membrane immunofluorescence but not by cytotoxic test. Both antisera cross-reacted with a subline of P1798 resistant to corticoids and asparaginase. These results establish the value of modified tumor cells in stimulating a protective immune response, even in a tumor-host system of minimal natural immunological responsiveness.

¹ This investigation was supported by USPHS Research Grant CA 12089 from the National Cancer Institute.

Received 3/27/74. Accepted 8/12/74.