Antitumor activity of T cells generated from lymph nodes draining the SEA-expressing murine B16 melanoma and secondarily activated with dendritic cells.
The successful use of tumor-draining lymph nodes (TDLN) as a source of effector cells for cancer immunotherapy depends largely on the immunogenicity of the tumor drained by the lymph nodes as well as the methods for secondary in vitro T cell activation and expansion. We transferred the bacterial superantigen staphylococcal enterotoxin A (SEA) gene into B16 murine melanoma tumor cells, and used them to induce TDLN (SEA TDLN) in syngeneic hosts. Wild-type (wt) TDLN induced by parental B16 tumor was used as a control. In vitro, SEA TDLN cells proliferated more vigorously, produced more IFN gamma and demonstrated higher CTL activity than wt TDLN cells when activated with anti-CD3/anti-CD28/IL-2. In vivo, SEA TDLN cells mediated tumor eradication more effectively than similarly activated wt TDLN cells (p<0.01). Furthermore, use of dendritic cells (DC) plus tumor antigen in vitro in addition to anti-CD3/anti-CD28/IL-2 stimulation further amplified the immune function and therapeutic efficacy of SEA TDLN cells. DC-stimulated SEA TDLN cells eliminated nearly 90% of the pulmonary metastasis in mice bearing established B16 melanoma micrometastases. These results indicate that enforced expression of superantigen SEA in poorly immunogenic tumor cells can enhance their immunogenicity as a vaccine in vivo. The combined use of genetically modified tumor cells as vaccine to induce TDLN followed by secondary stimulation using antigen-presenting cells and tumor antigen in a sequential immunization/activation procedure may represent a unique method to generate more potent effector T cells for adoptive immunotherapy of cancer.
Yu
Jiyun
J
Institute of Basic Medical Sciences, Academy of Military Medical Sciences, Beijing, China.
Tian
Rong
R
Xiu
Bingshui
B
Yan
Jinqi
J
Jia
Rui
R
Zhang
Liang
L
Chang
Alfred E
AE
Song
Hongbin
H
Li
Qiao
Q
D000818:Animals; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D004768:Enterotoxins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008198:Lymph Nodes / Q000166:cytology*; D008546:Melanoma, Experimental / Q000628:therapy*; D051379:Mice; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*
D004768:Enterotoxins; C026066:enterotoxin A, Staphylococcal