Chemotherapy enhances recombinant lipoimmunogen-based antitumor immunity against cervical cancer

[[abstract]]Although CTLs play a major role in eradicating cancer cells during immunotherapy, the development of immune escape often limits the success of such therapy. Therefore, the simultaneous induction of CTLs against cancer and administration of chemotherapy would be feasible to overcome the limitation. The recombinant lipoprotein consisting of inactive E7 (E7m) biologically linked to a bacterial lipid moiety (rlipo-E7m) induces the maturation of mouse bone marrow-derived dendritic cells through toll-like receptor 2 (TLR2), E7-specific cytotoxic T lymphocytes (CTLs) responses and inhibits tumor growth. The large tumor (> 10 mm diameter) was regressed when treated with rlipo-E7m and TLR9 agonist (oligodeoxynucleotide, CpG ODN). In addition, the combinations inhibit local immunosuppressive cells number (MDSCs, TAM and Tregs) and increase CTLs number in tumor infiltration. However, the tumor grew again at ∼ 50 days after tumor implantation. To improve the therapeutic effects of rlipo-E7m/CpG, cisplatin or gemcitabine was combined to treat large tumor. We found that the combinations increase the survival time of the tumor-bearing mice. The promising approach may be applied to other tumor antigen for other cancer immunotherapy