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Projects / Programmes source: ARIS

Advanced immunological drugs and cell-based approaches in pharmacy

Periods
January 1, 2022 - December 31, 2027
Research activity

Code Science Field Subfield
1.09.00  Natural sciences and mathematics  Pharmacy   
3.01.00  Medical sciences  Microbiology and immunology   

Code Science Field
3.01  Medical and Health Sciences  Basic medicine 
1.04  Natural Sciences  Chemical sciences 
Keywords
next-generation vaccines, adjuvants. immunotherapeutics, medicinal chemistry, advanced delivery systems, immunopharmacology, cancer immunotherapy, allergen immunotherapy, cell therapy, mesenchymal stem cells, cancer, allergies, immunotoxicology
Evaluation (rules)
source: COBISS
Points
4,532.75
A''
893.44
A'
2,724.79
A1/2
3,404.78
CI10
6,824
CImax
230
h10
45
A1
16.79
A3
1.72
Data for the last 5 years (citations for the last 10 years) on May 17, 2024; A3 for period 2018-2022
Data for ARIS tenders ( 04.04.2019 – Programme tender, archive )
Database Linked records Citations Pure citations Average pure citations
WoS  275  7,427  6,612  24.04 
Scopus  283  8,297  7,431  26.26 
Researchers (13)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  23598  PhD Tomaž Bratkovič  Pharmacy  Researcher  2022 - 2024  236 
2.  53585  PhD Črt Dragar  Pharmacy  Junior researcher  2022 - 2024  38 
3.  58034  Klemen Gnidovec  Pharmacy  Junior researcher  2023 - 2024 
4.  32034  PhD Martina Gobec  Oncology  Researcher  2022 - 2024  179 
5.  52379  PhD Samo Guzelj  Pharmacy  Researcher  2023 - 2024  22 
6.  26496  PhD Žiga Jakopin  Pharmacy  Head  2022 - 2024  195 
7.  56838  Špela Janež  Pharmacy  Junior researcher  2022 - 2024 
8.  24402  PhD Petra Kocbek  Pharmacy  Researcher  2022 - 2024  295 
9.  33908  PhD Urban Košak  Pharmacy  Researcher  2022 - 2024  58 
10.  25096  PhD Mojca Lunder  Pharmacy  Researcher  2022 - 2024  255 
11.  55140  Lara Smrdel  Pharmacy  Researcher  2023 - 2024  13 
12.  54787  Veronika Weiss  Pharmacy  Junior researcher  2022 - 2024 
13.  32306  PhD Janja Zupan  Metabolic and hormonal disorders  Researcher  2022 - 2024  110 
Organisations (1)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0787  University of Ljubljana, Faculty of Pharmacy  Ljubljana  1626973  17,216 
Abstract
The development of safe and effective vaccines against infectious diseases such as SARS-CoV2, Zika, malaria, Ebola and the emerging zoonoses is a major goal in global public health. Also, cancer clearly remains one of the leading causes of disease and mortality worldwide. Recent advances in immunotherapy and cell therapy established them as potential new modalities for treatment of cancer. Immunotherapy is also an important approach in the causal treatment of allergies. These major topics are not covered well by the existing research programmes in Slovenia. These research areas, which are always among the main priorities of EU funding schemes, have been somewhat neglected and underfunded. To that end, we proposed a new programme, centered around the immune system and based on four basic work-packages: (i) Next-generation vaccines; (ii) Immunotherapy and cell therapy of cancer; (iii) Immunotherapy and cell therapy of allergies; and (iv) Immunotoxicology. Within the framework of the first platform, we will cover all stages of development of innovative vaccines (classic vaccines, next-generation vaccines, tumor vaccines, vaccines for immunotherapy of allergies): expression of proteins, DNA or RNA and their isolation and purification; development of synthetic adjuvants; development of formulations or advanced delivery systems and labeling with ligands for targeted delivery; in vitro immunopharmacological evaluation; in vivo preclinical evaluation of efficacy and safety of vaccines. In the second platform, immunotherapy and cell therapy as advanced approaches for cancer treatment, we will focus on the: development of innovative innate immune agonists for cancer treatment, use of mesenchymal stem cells (MSC) as a delivery system for targeting cancer tissues, study of new synergistic drug combinations with anticancer activity and in vitro evaluation of anticancer activity. The third platform relies on the use of immunotherapy and the immunosuppressive action of MSCs in the treatment of allergies. In the scope of the platform we will study the immunotoxic effects of small molecules in vitro and evaluate the immunogenicity of proteins.
Significance for science
The proposed RP will provide new insights on how to harness the strength of immune system to tackle important therapeutic areas with impacts at several levels. Its public health relevance is highly significant since our results are expected to: (i) expand the therapeutic arsenal to fight infections with next-generation vaccines, (ii) establish novel therapeutic modalities for treatment of cancer, (iii) establish novel therapeutic modalities for treatment of allergies and (iv) unravel the mechanism of immunotoxicity of compounds and environmental pollutants. Our long-term goal is to improve vaccine performance using a chemical strategy of directing the immune system in terms of breadth, intensity, durability and the type of response to achieve an optimal response against an antigen of interest. Only a few vaccine adjuvants are currently on the market in the US and Europe. In the scope of this RP, we will identify structural features pivotal for adjuvant activity and construct innovative custom-tailored and safe adjuvants. We will be the first to address several molecular combinations merged into a single compound in the form of multivalent conjugates, which have been, to date, only considered separately, neglecting the importance of subtle interactions of our immune system. These conjugates will engage several targets within the same cell, thus gaining access to unprecedented synergies. The elucidation of hierarchies of innate immune signaling pathways will be pivotal in advancing our understanding of principles governing in vivo interactions of innate immune receptors. The library of rationally designed innovative conjugates with custom-tailored properties will be useful as adjuvants not only in prophylactic/therapeutic vaccines for infectious diseases but also in cancer vaccines. Of note, the synthesized conjugates will also be able to harness the synergies of innate immune system to eliminate tumors and provide long-term antitumor immunity. The acquisition of new knowledge and understanding on which signaling pathways need to be mobilized simultaneously to achieve antitumor properties will act as a springboard for the development of novel anti-cancer drugs. Moreover, mesenchymal stem cells (MSCs) created immense opportunities to take a step forward in treatment of allergies and cancer. Studies have clearly shown that MSC-based therapies are indeed effective in treatment of allergic diseases, while their role as an advanced delivery system carrying an anti-cancer drug payload has also been highlighted and confirmed in preclinical models. Fostering scientific excellence, which is one of major goals of the proposed RP, will contribute to affirmation of Slovenian science; the results will be diffused on several levels. First off, they will lead to joint publications in top-tier journals (consistent with the participants’ track records). Further, we will disseminate our results on several levels, via conference communications and posters at national and international levels as well as via project web-page to reach as wide a scientific audience as possible. Dissemination of results to students and general population through media as one of priority outreach activities will contribute to popularization of science among young people and in the society. The RP results will be communicated also at the highschool level to raise an interest among gymnasium graduates, so that they will consider university studies in pharmacy and other related natural sciences. Outreach activities in which our group has been involved up until now should clearly ensure appropriate diffusion of the results to the public in the future. In summary, the results of the proposed research programme will be of great scientific importance as it will pave the path for new approaches to treat diseases by boosting the immune system. Notably, the results obtained during the course of this RP are expected to impact significantly several related scientific disciplines, including medicinal chemistry, biotechnology, immunology and oncology.
Significance for the country
Discovery of innovative drugs and/or therapeutic modalities and introducing them to the market is a way to ensure a sustained growth to the Slovenian pharmaceutical industry, the major player of Slovenian economy. The current generic nature of the Slovenian pharmaceutical industry does not preclude its evolution into research-oriented pharmaceutical industry and education of creative and competent scientists in research programme will importantly contribute to this important socioeconomic task. The proposed research programme will generate new and master the existing knowledge both of which are of paramount importance for sustained development of pharmaceutical industry and drug–oriented research in Slovenia. Young scientists educated in the proposed RP will gain competences for independent creative work in pharmaceutical industry as well as at universities, other research institutes and governmental agencies. Although the majority of the envisaged results of proposed RP can be regarded as basic science, some results will surely have the potential to be applied directly in new drug development in pharmaceutical industry on a competitive level through licensing. Novel compounds resulting from the proposed RP can be a good starting point for development of innovative medicines in cooperation of the Slovenian and international pharmaceutical industry. It should also be acknowledged that this RP may have a tangible impact at the business level. Data gained through the proposed RP might seed the R&D of a future spin-off company. It is worth mentioning that cellular therapies are the next major advancements in transforming healthcare. The global stem cells market, including MSCs, was estimated at almost 7 billion USD in 2016. Similarly, immunotherapy has been predicted to provide the backbone of up to 60% of cancer therapies within the next decade. Several biomedical companies recognized this potential and are consequently expanding their immunotherapeutic and cellular therapy portfolios. Infectious disease pandemics and cancer carry tremendous individual and socioeconomic burden. The RP is therefore of significant clinical relevance. Millions of infections worldwide each year could be avoided using suitable vaccines. In particular, the unknown but quickly emerging zoonotic diseases, which can be transmitted to humans, are a significant global public health concern. Moreover, at the animal health and economic levels, the proposed RP is expected to add great value too. Certain zoonoses are highly infectious and affect livestock and wildlife with serious economic loss. Some of them are difficult to treat with antibiotics and no effective vaccine exists to prevent human infection. Any novel treatments are therefore going to be profitable for agriculture, animal health and economy. Cancer is the second most common form of death from illness and accounts for almost 10 million deaths per year globally. The economic impact of cancer is increasing each year; the cost exceeded 100 billion euros in 2020. Therefore, any novel approach to tackle this problem is of paramount importance. Given the fact that cancer is a set of a complex group of diseases, the necessity for personalized treatment is imperative. Cancer pharmacotherapy is hard to achieve; the commonly used anti-cancer drugs also suffer from toxicity and resistance. An increasing body of evidence shows that anti-tumor immunity has the potential to eradicate cancer cells, which is expected to revolutionize cancer treatment. The use of MSCs to selectively deliver anti-cancer payloads to cancer cells will contribute to the development of advanced drug delivery systems. The novel MSC-based therapies will bring new hope to cancer patients by offering highly effective anti-cancer treatments in a personalized manner. The collective efforts of the proposed RP are aimed at generating a safe and effective cancer therapy that will improve survival and quality of life. Also, allergic diseases are one of the most prevalent chronic illnesses. Allergic rhinitis alone accounts for over 11 billion dollars of treatment-associated costs. Being a predictor and risk factor for asthma further expands its economic impact. Current pharmacotherapy of allergies only temporarily inhibits the inflammation and causes various adverse effects with chronic use. Allergen immunotherapy is the only modality capable of modifying the immune response to allergens thus preventing recurrence of disease in the long-term. MSC-based therapy offers another promising approach uniquely tailored to treat allergic diseases. These new modalities capable of permanently treating allergies could therefore have a profound impact on patients’ health as well as on the reduction of the economic burden associated with those diseases. A successful use of MSCs could also pave the way for MSC-based therapies of other indications to reach the clinic. Information gained on harmful effects of some chemicals on immune system will be a very important contribution to the preparation of guidelines, directives and regulations for the harmonized assessment and risk management at national and European level, which will significantly contribute to the protection of public health. The obtained toxicological profiles will also directly impact several environmental policies, including those on emissions reduction, on monitoring efforts or clean-up of contaminated sites. The research generated by RP will strengthen the existing link between the collaborating research groups, thereby fostering long-term partnership. It will contribute to the integration of Slovenian science into the international research community and its promotion. Obtained results will serve as a driving force to start scientific contacts with other prominent groups in order to work on grant proposals in the future. We plan to apply for international funding, such as Horizon Europe, which is in accordance with the national strategy.
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