By developing advanced methods of prevention and therapy – immunotherapy, highly effective in the treatment of cancer, allergies and chronic degenerative diseases (Alzheimer’s disease), we aim to significantly improve the health of the population, thus improving the quality of life and reducing the costs of medical services, for specific disorders.
At the same time, new diagnostic and targeted therapy kits for allergic diseases will be developed using specific recombinant epitopes. Knowledge gained from fundamental research in this area will later serve to establish reproducible work procedures that will guide GMP cell production for clinical trials. At the OncoGen Center, we aim to create a nucleus of scientific competence at European standards for personalized immunotherapy.
a) Chimeric antigen receptor in onco-immunotherapy using Natural killer (NK) cells
Natural Killer Cells (NK) represent a population of lymphocytes that are attractive to cancer immunotherapy because of their ability to lyse tumor targets without prior sensitization and without the need for compatibility of human leukocyte antigens as opposed to T lymphocytes. Chimeric antigen receptors (CAR) represent a new tool for the development of adoptive immunotherapy by enhancing the targeting and activation of lymphocytes against malignant tumors. CAR may be expressed in lymphocytes to create a large number of antigen-specific cells which, following recognition and binding to tumor cells expressing the antigen, will mediate cytotoxicity and cytokine production.
The proposed project will have a direct impact on the treatment of patients with cancer, currently incurable in Romania, and abroad. In the event of success, the project will result in a new, safe and effective treatment option for patients with untreated conditions. While the project aims to establish cell-based personalized treatments in patients with acute B-cell leukemia by generating anti-CD19 specific CARs, the technology can be easily extended to other tumor antigens. Compared to T lymphocytes, we assume that re-directed NK cells will be suitable for the treatment of solid cancers as well. The most common cancers in Romania, such as ovarian cancer, colon cancer, breast cancer and lung cancer, will be an ideal target. Detection of specific tumor antigens will go along with the need for an accurate diagnosis and screening of appropriate tumor antigens that are expressed by the patients’ cancerous cells.
The primary objective of this project proposal is to follow a unique approach and develop new CARs that are especially suited to NK cell therapies, which represent the latest anti-tumor personalized therapy. We expect this project to produce international patent applications, which will ultimately translate into the marketing of this technology in Romania and abroad. Knowledge gained from fundamental research in this field will later serve to establish reproducible working procedures that will guide GMP cell production for clinical trials. The project intends to create a nucleus of scientific competence at European standards for personalized antitumor therapy at the OncoGen Center.
b) Innovative strategies for the prevention, diagnosis and therapy of respiratory diseases induced by ambrosia pollen (INSPIRED)
The main objective of the INSPIRED project is the development of a new diagnostic kit based on the use of recombinant allergens, specific for patients allergic to Ambrosia, which will better target the therapy of the disease and creating a high-level scientific excellence in the application of advanced technologies based on recombinant allergens within the OncoGen research center.
Through the implementation of the INSPIRED project, which addresses new themes in the priority areas, Romania’s research and economic competitiveness will increase, because it is aimed at developing advanced technologies based on recombinant allergens, which are at an early stage even in the rest of Europe. The design of hypoallergenic molecules derived from allergens, based on new technologies to obtain recombinant molecules, will allow the development of diagnostic tests based on recombinant allergens, applicable to medical services. Allergen quantification tests can also be used to measure the amount of allergen in the environment, thus contributing to improved predictions of pollinic concentrations and thus to more effective avoidance of allergens. For the development of allergen-specific vaccines, the identification of allergens and the development of prototype molecules will be followed and at a later stage their clinical effectiveness in European projects will be tested, including testing in partnership with the pharmaceutical industry.
c) New biomarkers and therapeutic strategies in immunosensence and immunosensence associated with Alzheimer’s disease
Immunosenescence is defined as the progressive alteration of the morphological and functional appearance that occurs in the immune system during the ageing process.
The specific objectives of this project are:
- Defining the status of immunosenescence by introducing new cellular biomarkers with specificity for this process.
- Characterization of proliferative potential, degree of apoptosis, and ability to generate the reactive oxygen species of the T lymphocyte subpopulation defined by new cell biomarkers.
- Defining the status of immunosenescence by introducing new serological markers.
- Defining the immunosenescence associated with Alzheimer’s disease in clinical dementia diagnosed and in prodromal stages (pre-dementia) by introducing new biomarkers specific to this pathology.
- Exploring new immunomodulatory therapeutic strategies in immunosenescence and immunosenescence associated with Alzheimer’s disease.
- The expected impact of this project is related to the significant development of the level of knowledge in this area, regarding the mechanisms and manifestations of immunosenescence and immunosenescence associated with Alzheimer’s disease. The application research directions of this project are directed towards diagnostic and therapeutic strategies, with the final result of this project being a set of new diagnostic and therapeutic recommendations for these conditions.