Projects / Programmes
Editing of immunosurviellance with the whole cell tumor vaccines and CpG ODN
| Code |
Science |
Field |
Subfield |
| 3.04.00 |
Medical sciences |
Oncology |
|
| Code |
Science |
Field |
| B520 |
Biomedical sciences |
General pathology, pathological anatomy |
| B200 |
Biomedical sciences |
Cytology, oncology, cancerology |
experimental oncology, tumor immunology, tumor vaccine, dendritic cells, CpG ODN
Researchers (8)
Organisations (1)
| no. |
Code |
Research organisation |
City |
Registration number |
No. of publicationsNo. of publications |
| 1. |
0302 |
Institute of Oncology Ljubljana |
Ljubljana |
5055733000 |
15,471 |
Abstract
Antitumor immunity is a complex network of activities of the effectors of the innate as well as of the acquired immunity. The role of innate immunity in recognition and elimination of tumor cells has been for a longer period of time inexcusably underestimated, yet lately it became clear that specific effectors such as B and T lymphocytes depend to a great extent upon the activity of phagocytic cells, upon the adequate presentation of tumor antigens and co-stimulatory molecules by antigen presenting cells (APC), as well as upon the production of immunostimulatory cytokines. In the decade since the discovery that mouse B cells respond to certain unmethylated CpG dinucleotides in bacterial DNA, a specific receptor for these 'CpG motifs' has been identified, Toll-like receptor 9 (TLR9), and a new approach to immunotherapy has moved into the clinic based on the use of synthetic oligodeoxynucleotides (ODN) as TLR9 agonists. CpG ODN have been described to function as natural adjuvants because they promote professional APC function and co-stimulate lymphocytes. The majority of studies of the immune effects of CpG ODN to date have been carried out on mammals where they are proving very successful at stimulating innate and adaptive immune responses in a variety of species as well as protecting them from bacterial, viral and protozoan pathogens.
The proposal of the study is aimed at assessing the ability of CpG ODN class C in combination with irradiated tumor cells to trigger the antitumor immunity (innate and acquired) in the experimental tumor model – i.p. B16F1. Our research interest is orientated into three major parts: assessment of preventive effect of the vaccine, assessment of therapeutic effect of the vaccine, and determination of some mechanisms and major effectors involved in the antitumor immunity triggered by this kind of vaccine.
Significance for science
The aim of the project was to create an effective tumor vaccine that would be promising enough for clinical evaluation. With this purpose we created the tumor vaccine composed of irradiated singeneic tumor cells and synthetic oligodeoxynucleotides containing CpG motifs class C (CpG ODNs). As to our knowledge, in our study the antitumor preventive and therapeutic effect as well as some mechanisms of action of the vaccine composed of CpG ODN class C and irradiated tumor cells were for the first time more accurately described. It was demonstrated that CpG ODN are capable of stimulating the DCs to activate T lymphocytes nonspecifically, while for the specific activation also the presence of tumor antigens is required. Vaccine composed of CpG ODN class C and irradiated tumor cells powerfully triggers the immune system to prevent tumor development. By this vaccine, the APCs (including DCs) are manipulated to differentiate and to activate the primary and the secondary immune response against tumor cells. When an adequate number of APCs is affected then the long-lasting immunity is achieved. The vaccine is also therapeutically useful but predominately for smaller tumor masses.
The activity of the tumor vaccine was followed also at the molecular level. Through investigating the gene expression of various “immunological genes” in MNC, we demonstrated a significantly enhanced expression of genes coding for IL-15, IL-18, protein kinase C – delta (Prkcd) as well as protein tyrosine phosphatase (Ptprc).
The future application of this kind of vaccine is expected to be as an adjuvant therapy after the removal of the predominant tumor mass.
Significance for the country
Proceeding from the planned objectives of preclinical trials - creation of effective tumor vaccine composed of irradiated tumor cells and CpG ODN as maturation signals for DC, verification of certain basic mechanisms of action of the tumor vaccine - we can anticipate the application of results of the proposed project in Republic of Slovenia in areas of:
- basic immunology (novel findings concerning the activation of immune system; novel findings concerning autoimmunity),
- diagnostics (developing procedures for follow up of effectiveness of vaccine preparation and activity offers possibilities for development of novel diagnostic methods),
- cancer treatment (promising preclinical results can be after standardization transferred into clinical research),
- pharmaceutical industry (certain procedures of preparation as well as results of vaccine effectiveness can be interesting also for pharmaceutical industry).
Most important scientific results
Annual report
2008,
2009,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2008,
2009,
final report,
complete report on dLib.si
