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Projects / Programmes source: ARIS

Autologous immunohybridomas and advanced treatment of stage II and III triple-negative breast cancer

Research activity

Code Science Field Subfield
3.01.00  Medical sciences  Microbiology and immunology   

Code Science Field
3.01  Medical and Health Sciences  Basic medicine 
Keywords
Autologous cell vaccine; monocyte-derived dendritic cells; immunohybridomas; triplenegative breast cancer; advanced therapy; experimental clinical testing
Evaluation (rules)
source: COBISS
Points
4,839.78
A''
812.55
A'
2,212.53
A1/2
3,262.72
CI10
12,376
CImax
1,012
h10
46
A1
17.11
A3
5.6
Data for the last 5 years (citations for the last 10 years) on April 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  572  17,152  14,332  25.06 
Scopus  534  18,715  15,810  29.61 
Researchers (19)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  16303  PhD Simona Borštnar  Oncology  Researcher  2021 - 2024  492 
2.  52511  Luka Dobovišek  Medical sciences  Researcher  2021 - 2024  31 
3.  32034  PhD Martina Gobec  Oncology  Researcher  2021 - 2024  177 
4.  18548  PhD Helena Haque Chowdhury  Neurobiology  Researcher  2021 - 2024  155 
5.  01302  PhD Matjaž Jeras  Biotechnology  Head  2021 - 2024  363 
6.  15666  PhD Marko Kreft  Neurobiology  Researcher  2021 - 2024  684 
7.  34385  PhD Jasna Lojk  Metabolic and hormonal disorders  Researcher  2021  68 
8.  57310  Ines Medved Palčar  Pharmacy  Researcher  2023 - 2024 
9.  25174  PhD Marina Mencinger  Medical sciences  Researcher  2021 - 2024  80 
10.  54060  Tanja Ovčariček  Medical sciences  Researcher  2021 - 2024  78 
11.  37274  Miha Pate  Neurobiology  Researcher  2021 - 2024 
12.  27747  PhD Samo Pirnat  Microbiology and immunology  Researcher  2021 - 2024  15 
13.  54114  Erika Rus  Neurobiology  Researcher  2021 - 2024 
14.  55140  Lara Smrdel  Pharmacy  Researcher  2022 - 2024  11 
15.  31572  PhD Saša Trkov Bobnar  Microbiology and immunology  Researcher  2021  56 
16.  52377  Taja Zore  Pharmacy  Researcher  2021 - 2024  13 
17.  03702  PhD Robert Zorec  Neurobiology  Researcher  2021 - 2024  802 
18.  38244  PhD Tomaž Mark Zorec  Medical sciences  Researcher  2022 - 2024  39 
19.  32306  PhD Janja Zupan  Metabolic and hormonal disorders  Researcher  2021 - 2022  110 
Organisations (4)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0302  Institute of Oncology Ljubljana  Ljubljana  5055733000  15,447 
2.  0381  University of Ljubljana, Faculty of Medicine  Ljubljana  1627066  48,195 
3.  0787  University of Ljubljana, Faculty of Pharmacy  Ljubljana  1626973  17,157 
4.  1683  Celica BIOMEDICAL  Ljubljana  1506854  1,782 
Abstract
Breast cancer (BC) is a significant and common disease with a negative effect prevalently on women health, and the second most deadly type of cancer in females. BC is a highly heterogeneous disease due to its diverse morphological features, variable clinical outcomes and responses to currently available therapeutic options. Due to its high degree of heterogeneity, BC cannot be viewed as a single disease, but is rather classified in three subtypes that are more homogeneous, i.e.: hormone (estrogen and progesterone) receptor positive, Her2-positive and triple-negative BC (TNBC), which is characterized by the lack of estrogen and progesterone receptors and HER2 protein expression. TNBC accounts for approximately 10 – 15% of all BCs and is characterized by aggressive behavior, a trend to early relapse and metastatic spread to lungs, liver and central nervous system, as well as by poorer survival. In a majority of TNBC patients, neoadjuvant chemotherapy is the standard treatment followed by surgery and radiotherapy. In approximately 30% of TNBC patients, complete remission (CR) is achieved with neoadjuvant therapy, which correlates with excellent prognosis. On the other hand, more than 50% of patients without pathologic complete remission (pCR) develop distant metastases, the majority of them within 2 years after diagnosis. The median overall survival (mOS) for metastatic TNBC is poor (one year only). As current basic treatment options in both, early and metastatic TNBC are limited to chemotherapy, new effective therapies are urgently needed for better management of the disease. Immunotherapy with immune checkpoint inhibitors, which interrupt tumor-based suppression of specific anti-tumor immune cell responses, became one of the promising strategies in TNBC treatment, being able to improve the survival rate of these patients. In numerous clinical studies evaluating the use of monoclonal antibodies inhibiting immune checkpoints (CTLA-4, PD-1 and PD-L1) in TNBC patients, atezolizumab (monoclonal antibody against PD-L1) proved to be the most effective, therefore it was introduced into the first line treatment of metastatic or inoperable locally advanced TNBC. As TNBC is a proven immunogenic type of cancer, we intend to develop and clinically test autologous immunohybridoma (aHyC) vaccines, made of electrofused monocyte-derived dendritic cells (DCs) and irradiated tumor cells (TCs), for each eligible patient. In this way we aim at equipping DCs, being the most effective antigen-presenting cells, with a whole array of tumor expressed antigens that would, following their subcutaneous delivery to areas of tumor proximal lymph nodes, evoke and boost specific anti-tumor T-cell responses. The vaccines will be administered to eligible stadium II and III TNBC patients, 3-times every 2-3 weeks, following the termination of the first line chemotherapy of metastatic disease. Along with that, we will take advantage of optimal positive effects of each particular chemotherapeutic applied, on tumor microenvironment, weakening its immunosuppressive impact on anti-tumor immune effector cells. Additionally, we intend to (at each vaccination), modulate the immune system of patients with unspecific adjuvant proinflammatory (Th1) stimulation, for example by using alloantigens, already previously tested by us in a clinical setting, thereby increasing the efficiency of the pre-existing, as well as de novo aHyC-induced anti-tumor immune responses. The primary objective of our research will be to examine the feasibility and safety of aHyC vaccination in stadium II and III TNBC patients, and the secondary to determine their progression-free and overall survial.
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