Owing to their capacity to induce and sustain immune responses, dendritic cells (DC) represent attractive vectors for immunotherapy. Yet, the optimal strategies for antigen delivery remain to be determined. Trials up to date utilized MHC class I restricted peptides thus limiting the responses to CTL only. In contrast, the use of unfractionated tumor material may provide both MHC class I and class II epitopes leading to a diverse immune response. Here we show that immature monocyte derived DC (MDC) phagocytose the bodies of killed breast carcinoma (BrCa) cell lines, HCC 1806 and MCF-7. Tumor cells are killed either by treatment with anti-Fas antibody following CHX sensitization or gamma-irradiation/serum starvation following TNF sensitization. DC that captured killed BrCa cells can present their antigens to autologous T cells as demonstrated by CD4+ and CD8+ T cell proliferation. Furthermore, BrCa bodies loaded DC elicit CTL lines in 3 weeks culture. These CTL lines are able to kill BrCa cells used for immunization, but neither the NK-sensitive K562 nor other tumor cells including another BrCa cells, melanoma or prostate cell lines. Induction of CTL differentiation is dependent on CD4+ help. Indeed, peripheral blood lymphocytes (PBL) depleted of CD4+ T cells do not yield BrCa-specific CTL. Thus, loading DC with killed BrCa cells provides both MHC class I and helper epitopes leading to a diverse anti-tumor immunity. This represents a novel approach for development of DC based vaccination protocols in breast cancer traditionally viewed as a non immunogenic tumor.
|Original language||English (US)|
|Issue number||11 PART II|
|State||Published - Dec 1 2000|
ASJC Scopus subject areas
- Cell Biology