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Therapeutic and Immunological Response of Mice with Meningeal Leukemia (L1210) to Challenge with an Antifolic-resistant Variant

( Drug Evaluation Branch, Cancer Chemotherapy, National Service Center, and Pathologic Anatomy Branch, National Cancer Institute,^* Bethesda, Maryland)

Augmentation of the therapeutic effectiveness of 3'-bromo-5'-chloroamethopterin (BCM) against the BCM-resistant variant of leukemia L1210 was demonstrated in mice given preinoculations intracerebrally of the sensitive parental line of leukemia L1210. Substantial increases in survival time were obtained, and in some cases these increases were almost as extensive as those observed when mice with sensitive leukemia L1210 alone were treated. The results indicated that the defense mechanism of the host in response to the preinoculation of L1210 contributed to the therapeutic efficacy of the drug against the resistant variant.

Mice immunized with x-radiated leukemia L1210 were capable of suppressing both subcutaneous and intracerebral inoculations of L1210. Substantial increases in survival time occurred, and several tumor-free survivors were obtained. Pathological study of meningeal leukemia showed that the leukemic deposits tended to be more localized in the immunized animals than in the nonimmunized animals. Leukemic cell infiltration into the retro-orbital tissues produced proptosis of the eyes in a few of the immunized mice.

When immunity was induced by the preinoculation of x-radiated leukemic cells there was a considerable enhancement of the effectiveness of chemotherapy. The combination of immunization and chemotherapy produced more extensive increases in survival time and a higher percentage of apparently tumor-free survivors than did either chemotherapy alone or immunization alone.

^* Formerly Biochemical Pharmacology.

Received 8/28/63.