Antitumor effects of anti-CD40/CpG immunotherapy combined with gemcitabine or 5-fluorouracil chemotherapy in the B16 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 macrophages 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. In this study we asked if the same chemotherapy regimens with GEM or 5-FU will enhance the antitumor effect of anti-CD40 and CpG. Using the model of B16 melanoma growing intraperitoneally in syngeneic C57BL/6 mice, we show that these GEM or 5-FU treatment regimens reduced MDSC in the peritoneal cavity of tumor-bearing mice. Treatment of mice with GEM or 5-FU did not significantly affect the antitumor function of macrophages as assessed in vitro. In vivo, treatment with these GEM or 5-FU regimens followed by anti-CD40/CpG resulted in antitumor effects similar to those of anti-CD40/CpG in the absence of GEM or 5-FU. Likewise, reduction of MDSC by in vivo anti-Gr-1 mAb treatment did not significantly affect anti-CD40/CpG antitumor responses. Together, the results show that the GEM or 5-FU chemotherapy regimens did not substantially affect the antitumor effects induced by anti-CD40/CpG immunotherapy.

• Authors: Xiaoyi Qu, Mildred A R Felder, Zulmarie Perez Horta, Paul M Sondel, Alexander L Rakhmilevich
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 17 Issue 4 Pg. 1141-7 (Dec 2013) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 24201083 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2013.

Chemical References

• Adjuvants, Immunologic
• Antimetabolites, Antineoplastic
• CD40 Antigens
• CPG-oligonucleotide
• Cancer Vaccines
• Nitrites
• Oligodeoxyribonucleotides
• Deoxycytidine
• Fluorouracil
• Gemcitabine

Topics

• Adjuvants, Immunologic (administration & dosage)
• Animals
• Antimetabolites, Antineoplastic (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• CD40 Antigens (immunology)
• Cancer Vaccines
• Cell Line, Tumor
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Female
• Fluorouracil (administration & dosage)
• Immunotherapy
• Macrophages (drug effects, metabolism)
• Melanoma, Experimental (metabolism, pathology, therapy)
• Mice
• Mice, Inbred C57BL
• Nitrites (metabolism)
• Oligodeoxyribonucleotides (administration & dosage, immunology)
• Skin Neoplasms (metabolism, pathology, therapy)
• Tumor Burden (drug effects)
• Gemcitabine