Background: Although cytotoxic T lymphocytes (CTLs) play a major role in cancer immunotherapy, the cancer-derived immunosuppressive cells often limits the success of such therapy. A recombinant lipoprotein (rlipo-E7m) with intrinsic TLR2 agonist activity containing a mutant form of E7 (E7m) and a bacterial lipid moiety has been demonstrated to induce robust CTL responses against tumors in mice. Furthermore, TLR9 agonist synergistically enhances anti-tumor immunity of rlipo-E7m and inhibits large tumor growth. However, the therapeutic effects are limited in the middle size tumor. In order to treat large tumor, we incorporated the chemotherapy into the recombinant immunogen-based cancer immunotherapy. Methods: In this study, we attempt to combine an anti-cancer drug, gemcitabine (Gem), with recombinant lipoprotein-based immunotherapy (rlipo-E7m/CpG) to treat advanced cancer. Mice-bearing large solid tumors (over 10 mm in diameter) were treated with different therapeutic regime consisting of rlipo-E7m/CpG and Gem. In addition, the tumor-infiltrating immunosuppressive cells were analyzed. Results: We observe that eradication of large tumors following administration of sub-optimal doses (75 mg/kg) of Gem at day 21, 24, and 27 as well as rlipo-E7m/CpG therapy at day 30 post tumor implantation. The combination therapy substantially reduces the numbers of immunosuppressive cells (CD11b + Gr-1 + , CD11b + F4/80+ and CD4 + CD25 + FOXP3+) and increases the tumor-infiltrating antigen-specific CD8+ T cells as compared to Gem or rlipo-E7m/CpG monotherapy.Conclusion: Administration of suboptimal doses of anti-cancer drugs with rlipo-E7m/ CpG ODN increased the survival time of tumor-bearing mice and reduces the number of immunosuppressive cells in tumor microenvironment. These findings suggested that this promising approach could be applied to other therapeutic cancer vaccines.
Date:
2015-11
Relation:
Annals of Oncology. 2015 Nov;26(Suppl. 7):vii79-vii105.
