Persistence of xenogenized vaccine cells in vivo

Trioma cell vaccination is a potent new immunotherapeutic strategy for the treatment of B cell neoplasias. It is based on the specific redirection of tumor antigens against surface receptors on professional antigen‐presenting cells (APC) that internalize antigens and present immunogenic peptides to T‐lymphocytes. Tumor cells are converted to trioma cells by fusion with xenogeneic hybridomas expressing an anti‐APC specificity. The trioma cell is a polyvalent vaccine that contains potentially all lymphoma‐derived antigens. Apart from the expression of the APC‐binding arm by the trioma cell, another requirement for successful tumor protection is the xenogeneic moiety of the trioma cells. We show that, despite their xenogenicity, trioma cells persist for extended periods in vaccinated animals. Trioma cells could be identified in spleens as long as about 12 weeks post vaccination. By using a suicide gene approach, trioma cells could partly be eliminated from immunized mice, whereby the antitumor effect was partly abrogated. We argue that not all trioma cells are immediately lysed in vivo and that the cell cycle of the remaining cells is arrested after having undergone few divisions. Trioma cells surviving in vivo may be instrumental for efficient induction of tumor immunity. © 2003 Wiley‐Liss, Inc.