Immune adjuvant and antitumor activity of baccatin III, a synthetic precursor of taxol (155.15)

Abstract

Abstract Baccatin III (BA-III), a precursor for the synthesis of taxol, is widely considered to be an inactive derivative of taxol. Here we show that baccatin III exerts immune adjuvant activity. When added to cultures of immature dendritic cells (DCs) generated from bone marrow cells with GM-CSF, baccatin III increased the expression of MHC II molecules and the allostimulatory activity of the DC. The immune adjuvant activity of baccatin III was examined in mice injected with a model antigen, OVA, emulsified with Freud’s incomplete adjuvant. Inclusion of baccatin III significantly increased the production of OVA-specific IgG, but not IgM. The in vivo combination effects of baccatin III and gemcitabine, an antitumor agent, were examined in mice bearing mammary carcinoma 4T1 cells. Combination of baccatin III with gemcitabin efficiently inhibited the tumor growth and the accumulation of myeloid derived suppressor cells (MDSC, CD11b+Gr-1+ cells), while increasing cellularity of CD4 T cells and CD8 T cells in the spleen, compared to baccaatin III only- or gemcitabine only-treated groups. These results demonstrate that baccatin III exerts immune adjuvant activity, and further show that baccatin III in combination with gemcitabine, a nucleoside analog used as chemotherapy, may be useful in the treatment of tumors that induce the accumulation of MDSCs.