Interleukin-12-secreting human papillomavirus type 16-transformed cells provide a potent cancer vaccine that generates E7-directed immunity

The development of a vaccine that would be capable of preventing or curing the (pre)cancerous lesions induced by genital oncogenic human papillomaviru ses (HPVs) is the focus of much research. Many studies are presently evalua ting vaccines based on the viral E6 and E7 oncoproteins, both of which are continually expressed by tumor cells. The success of a cancer vaccine relie s, in large part, on the induction of a tumor-specific Th1-type immunity. i n this study, we have evaluated the ability of B7-related and/or interleuki n-li! (IL-12)-expressing, non-immunogenic murine HPV16-transformed BMK-16/m yc cells, to achieve this goal, BMK-16/myc cells engineered to express surf ace B7-1 or B7-2 molecules remain tumorigenic in syngeneic BALB/c mice, sug gesting that expression of these molecules alone is not sufficient to induc e tumor regression. In contrast, mice injected with tumor cells engineered to secrete IL-12 remained tumor-free, demonstrating that IL-12 expression i s sufficient to induce tumor rejection, IL-12-secreting BMK-16/myc cells we re further shown to induce potent and specific long-term tumor resistance, even after irradiation. B7-1 was found to slightly but systematically impro ve anti-tumor immunity elicited by IL-12-secreting BMK-16/myc cells. Inject ion of irradiated B7-1/IL-12 BMK-16/myc cells generates longlasting, Th I-t ype, BMK-16/myc-directed immunity in tumor-resistant mice, These mice displ ay a memory-type, E7-specific, cell mediated immune response, which is pote ntially significant for clinical applications. (C) 1999 Wiley-Liss, Inc.