Tumor-cell vaccination induces tumor dormancy in a murine model of B-cell leukemia/lymphoma (BCL1).

Immunity to murine B-cell leukemia/lymphoma (BCL1) induced by multiple injections with irradiated tumor cells, prevented leukemia development in primary and adoptive transfer recipients despite long-lasting persistence of residual tumor cells. Detection of dormant BCL1 cells was carried out by PCR analysis using the VH-rearranged DNA sequence as a BCL1 clonal marker. Dormant tumor cells were detected > 250 days following immunity induction in 40% of spleens from healthy immune mice having no detectable symptoms of disease. Tumor dormancy was not abrogated by adoptive transfer of BCL1-containing splenocytes into syngeneic recipients, indicating that cell-mediated anti-tumor immunity contributes to maintenance of the tumor dormant state and prevents renewed tumor-cell growth. Splenocytes but not sera from immune mice conferred specific radiosensitive protection from a lethal dose of BCL1 cells included in cell mixtures transferred to secondary recipients. A therapeutic effect of transferred immune splenocytes was shown in BCL1-bearing mice, which remained disease-free for > 200 days after inoculation; nevertheless, dormant BCL1 cells were detected by PCR analysis in some of the surviving mice. Our results suggest that an efficient tumor-cell vaccine can lead to induction of tumor dormancy that can be maintained by a cell-derived mechanism for a long period of time.