ANTITUMOR EFFECTS OF ANTl-CD40/CPG IMMUNOTHERAPY COMBINED WITH GEMCIT ABINE OR 5-FLUOROURACIL CHEMOTHERAPY IN THE B 16 MELANOMA MODEL

Abstract

Our previous studies demonstrated that anti-CD40 mAb (anti-CD40) can synergize with CpG oligodeoxynucleotides (CpG) to mediate antitumor effects by activating myeloid cells such as macro phages in tumor-bearing mice. Separate teams have shown that chemotherapy with Gemcitabine (GEM) or 5-fluorouracil (5 -FU) can reduce tumor-induced myeloid-derived suppressor cells (MDSC) in mice. We asked if the same chemotherapy regimens with GEM or 5-FU will interfere with, or enhance, the antitumor effect of anti-CD40/CpG. Using the model of B 16 melanoma growing intraperitoneally in syngeneic C57BLl6 mice, we show that GEM or 5-FU treatment regiments either did not change or reduced, respectively, the number of MDSC in the peritoneal cavity of tumor-bearing mice. In vivo. GEM or 5-FU chemotherapy regimens did not substantially affect antitumor effects induced by anti-CD40/CpG immunotherapy.