Cooperative effects of Mycobacterium tuberculosis Ag38 gene transduction and interleukin 12 in vaccination against spontaneous tumor development in proto-neu transgenic mice

An approach to stimulating an immune response against tumors is to transduc e tumor cells with bacterial genes, which represent a "danger signal" and c an induct a wide immune response, Mycobacterium tuberculosis genes and thei r encoded proteins play a pivotal role in linking innate and cell-mediated adaptive immunity and represent ideal candidates as immune adjuvants for tu mor vaccines, The efficacy of a cancer vaccine, obtained hy transduction of a mammary tumor cell line with the M. tuberculosis Ag38 gene, was investig ated in female mice transgenically expressing the rat HER-2/neu proto-oncog ene, These mice spontaneously develop stochastic mammary tumors after a lon g latency period, The onset of spontaneous mammary tumors was significantly delayed in mice vaccinated with Ag38-transduced cells but not in mice vacc inated with non-transduced cells as compared with untreated mice, Protectio n from spontaneous tumor development was increased when mice were vaccinate d with the mycobacterium gene-transduced vaccine plus a systemic: administr ation of interleukin 12 (IL-12) at a low dose, Mice vaccinated with nontran sduced cells plus IL-12 developed tumors, with only a slight delay in tumor appearance as compared with the control group, Lymphocytes obtained from l ymph nodes of mice vaccinated with transduced cells secreted high levels of IFN-gamma. CD3(+)CD8(+) spleen cells derived from these mice responded to the tumor with IFN-gamma production. These data indicate the efficacy of a short-term protocol of vaccinations exploiting the adjuvant potency of a M. tuberculosis gene and low doses of IL-12 in a model of stochastic developm ent of mammary tumors. This adjuvant approach may represent a promising imm unotherapeutic strategy for cancer immunization.