Anti-tumour effects of exosomes in combination with cyclophosphamide and polyinosinic-polycytidylic acid.
We examined the anti-tumour activity of exosomes derived from dendritic cells (DCs) in combination with cyclophosphamide (CTX) and polyinosinic-polycytidylic acid sodium salt (poly I:C). DCs were pulsed with L1210 lymphocytic leukaemia cell antigen and lipopolysaccharide. The exosomes that the DCs secreted were purified. In vitro, the anti-tumour activity of exosomes was assessed by measuring their ability to induce spleen cell proliferation and the extent to which they induced spleen cells to kill L1210 cells. Poly I:C was able to induce DC maturation. DC-derived exosomes stimulated spleen cell proliferation and enhanced the cytotoxic effects of spleen cells in vitro. DC-derived exosomes, in combination with CTX and poly I:C, suppressed L1210 tumour growth in vivo and gave the greatest prolongation of survival time in tumour-bearing DBA2 mice. These findings suggest that this combination of a tumour vaccine, a conventional anti-cancer agent and a promoter of DC maturation might be a useful anti-cancer therapy.
Guo
F
F
Shanghai Number 6 Hospital, Shanghai [corrected] China.
Chang
C K
CK
Fan
H H
HH
Nie
X X
XX
Ren
Y N
YN
Liu
Y Y
YY
Zhao
L H
LH
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017690:Cell Transplantation; D003520:Cyclophosphamide / Q000494:pharmacology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004359:Drug Therapy, Combination; D055354:Exosomes / Q000276:immunology / Q000637:transplantation*; D007369:Interferon Inducers / Q000494:pharmacology*; D008136:Longevity / Q000187:drug effects; D051379:Mice; D008811:Mice, Inbred DBA; D009374:Neoplasms, Experimental / Q000628:therapy*; D011070:Poly I-C / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects
D018906:Antineoplastic Agents, Alkylating; D007369:Interferon Inducers; D003520:Cyclophosphamide; D011070:Poly I-C