Objectives:

By developing advanced methods of prevention and therapy - immunotherapies, which are extremely 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 at the same time reducing the costs of medical services in certain diseases.

At the same time, new diagnostic kits and targeted therapies for allergic diseases will be developed using specific recombinant epitopes. The knowledge gained from fundamental research in this area will later serve to establish reproducible working procedures that will guide the GMP production of cells for clinical trials. At the OncoGen Centre, we aim to create a core of scientific competence at European standards for personalized immunotherapy.

a) Chimeric antigen receptors in onco-immunotherapy using natural killer cells (CAR – T cells & CAR NK)

Short description:

Natural Killer (NK) cells represent a very attractive lymphocyte population for cancer immunotherapy due to their ability to lyse tumor targets without prior sensitization and without the need for human leukocyte antigen compatibility, in contrast to T lymphocytes. Chimeric antigen receptors (CAR) represent a new tool for the development of adoptive immunotherapy by increasing the targeting and activation of lymphocytes against malignant tumors. CAR can be expressed in lymphocytes to create large numbers of antigen-specific cells that, upon recognition and binding to antigen-expressing tumor cells, will mediate cytotoxicity and cytokine production.

The proposed project will have a direct impact on the treatment of cancer patients, who are currently incurable in Romania and abroad. If successful, the project will result in a new, safe and effective treatment option for patients with incurable conditions. While the project aims to establish personalized cell-based treatments for patients with acute B-cell leukemia, by generating specific anti-CD19 CARs, the technology can be easily extended to other tumor antigens. Compared to T lymphocytes, we hypothesize that redirected NK cells will also be suitable for the treatment of solid tumors. The most common cancers in Romania, such as ovarian cancer, colon cancer, breast cancer and lung cancer will be ideal targets. The detection of specific tumor antigens will go hand in hand with the need for correct diagnosis and screening for the appropriate tumor antigens that are expressed by the patients' cancer cells.

The main objective of this project proposal is to develop new CARs that are particularly suitable for NK cell therapies, which represent the latest personalized anti-tumor therapy. We expect this project to produce international patent applications, which will eventually lead to the commercialization of this technology in Romania and abroad. The knowledge gained from fundamental research in this area will later serve to establish reproducible working procedures that will guide the production of GMP cells for clinical trials. The project intends to bring scientific competence to European standards for personalized antitumor therapy at the OncoGen Center.

b) Innovative Strategies for the Prevention, Diagnosis and Therapy of Ambrosia Pollen-Induced Respiratory Disease (INSPIRED)

Short description:

The main objective of the INSPIRED project is the development of a new diagnostic kit based on the use of recombinant allergens, specific for ragweed allergic patients, which will better target the therapy of the disease and create high-level scientific excellence in the application of advanced technologies based on allergen recombinants from the OncoGen Research Center.

By implementing the INSPIRED project, which addresses new topics in priority areas, Romania's research and economic competitiveness will increase, as it aims to develop 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 for obtaining 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 allergens in the environment, thus contributing to improved predictions of pollen concentrations and thus more effective allergen avoidance. For the development of allergen-specific vaccines, the identification of allergens and the development of prototype molecules will be pursued, and in the later stage their clinical effectiveness will be tested through European projects, including testing in partnership with pharmaceutical industries.

c) Personalized vaccines in cancer and infectious diseases (DECODE)

Short description:

Objectives:

d) New biomarkers and therapeutic strategies in immunosenescence and immunosenescence associated with Alzheimer's disease

Short description:

Immunosenescence is defined as a progressive change in morphological and functional appearance that occurs in the immune system during the aging process.

The specific objectives of this project are:

• Defining the state of immunosenescence by introducing new cellular biomarkers with specificity for this process.
• Characterization of the proliferative potential, degree of apoptosis, and reactive oxygen species-generating capacity of T lymphocyte subpopulations defined by novel cellular biomarkers.
• Defining the status of immunosenescence by introducing new serological markers.
• Defining immunosenescence associated with Alzheimer's disease in diagnosed clinical dementia and in pre-dementia stages by introducing new biomarkers specific to this pathology.
• Exploring new immunomodulatory therapeutic strategies in immunosenescence and immunosenescence associated with Alzheimer's disease.
• The expected outcome of this project is the significant development of the level of knowledge in this field, regarding the mechanisms and manifestations of immunosenescence and immunosenescence associated with Alzheimer's disease. The applied research directions of this project are directed towards diagnostic and therapeutic strategies, the end result of this project is a set of new diagnostic and therapeutic recommendations for these conditions.