Intracerebral adoptive immunotherapy of a murine lymphoma antigenically altered by drug treatment in vivo.

Intracerebral tumor neutralization assay and adoptive immunotherapy with in vivo sensitized lymphocytes were done in immunodepressed mice challenged intracerebrally with L5178Y/DTIC lymphoma, a tumor subline antigenically altered by treatment with 5-(3,3-dimethyl-1-triazenyl)-1H-imidazole-4-carboxamide (DTIC) in vivo. Primary cytotoxic T-lymphocytes (CTL) were generated in vitro against L5178Y/DTIC cells with the use of splenocytes of histocompatible (BALB/cCr X DBA/2Cr)F1 donors. The extent of antitumor activity of CTL was evaluated by the measurement of tumor cell proliferation in the brain, as judged by the 125I-labeled 2'-deoxyuridine uptake values and by survival times of recipient mice. The results of the experiments showed: a) CTL were highly effective in inhibiting tumor growth when they were injected along with L5178Y/DTIC tumor cells in a Winn-type neutralization assay; b) the tumor inhibition mediated by CTL was specific, since no antilymphoma effects were detected when CTL sensitized against L5178Y/DTIC line were admixed with the parental L5178Y tumor or with other unrelated lymphoma cells; and c) local adoptive immunotherapy with CTL given on day 1, 3, or 5 after the intracerebral challenge with L5178Y/DTIC lymphoma substantially impaired tumor cell proliferation and significantly increased survival times of recipient leukemic mice.