Tumor vaccine composed of C-class CpG oligodeoxynucleotides and irradiated tumor cells induces long-term antitumor immunity

被引:11
作者
Cerkovnik, Petra [1 ]
Novakovic, Barbara Jezersek [2 ]
Stegel, Vida [1 ]
Novakovic, Srdjan [1 ]
机构
[1] Inst Oncol Ljubljana, Dept Mol Diagnost, Ljubljana 1000, Slovenia
[2] Inst Oncol Ljubljana, Dept Med Oncol, Ljubljana 1000, Slovenia
关键词
MEMORY T-CELLS; BONE-MARROW; METASTATIC MELANOMA; DENDRITIC CELLS; PHASE-II; RECEPTOR; ACTIVATION; RESPONSES; PEPTIDE; CANCER;
D O I
10.1186/1471-2172-11-45
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background: An ideal tumor vaccine should activate both effector and memory immune response against tumor-specific antigens. Beside the CD8+ T cells that play a central role in the generation of a protective immune response and of long-term memory, dendritic cells (DCs) are important for the induction, coordination and regulation of the adaptive immune response. The DCs can conduct all of the elements of the immune orchestra and are therefore a fundamental target and tool for vaccination. The present study was aimed at assessing the ability of tumor vaccine composed of C-class CpG ODNs and irradiated melanoma tumor cells B16F1 followed by two additional injections of CpG ODNs to induce the generation of a functional long-term memory response in experimental tumor model in mice (i.p. B16F1). Results: It has been shown that the functional memory response in vaccinated mice persists for at least 60 days after the last vaccination. Repeated vaccination also improves the survival of experimental animals compared to single vaccination, whereas the proportion of animals totally protected from the development of aggressive i.p. B16F1 tumors after vaccination repeated three times varies between 88.9%-100.0%. Additionally, the long-term immune memory and tumor protection is maintained over a prolonged period of time of at least 8 months. Finally, it has been demonstrated that following the vaccination the tumor-specific memory cells predominantly reside in bone marrow and peritoneal tissue and are in a more active state than their splenic counterparts. Conclusions: In this study we demonstrated that tumor vaccine composed of C-class CpG ODNs and irradiated tumor cells followed by two additional injections of CpG ODNs induces a long-term immunity against aggressive B16F1 tumors.
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页数:10
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