THE SCIENTIFIC DISCUSSION OF SOME ISSUES OF FEATURES AND CHALLENGES OF USING OF CAR-T CELLS IN IMMUNOTHERAPY

Nodar Sulashvili; Magda Davitashvili; Nana Gorgaslidze; Luiza Gabunia; Margarita Beglaryan; Nato Alavidze; Igor Seniuk; Vira Kravchenko; Nino Abuladze; Ketevani Gabunia; Marina Giorgobiani; Marika Sulashvili

doi:10.52340/gs.2024.06.04.24

Authors

Nodar Sulashvili Tbilisi State Medical University , Georgia https://orcid.org/0000-0002-9005-8577
Magda Davitashvili Iakob Gogebashvili Telavi State University , Georgia https://orcid.org/0009-0005-4213-6533
Nana Gorgaslidze Tbilisi State Medical University , Georgia https://orcid.org/0000-0002-4563-5224
Luiza Gabunia https://orcid.org/0000-0003-0856-2684
Margarita Beglaryan Yerevan State Medical University, Georgia https://orcid.org/0000-0003-3697-6390
Nato Alavidze East European University, Georgia https://orcid.org/0000-0001-6695-5924
Igor Seniuk National University of Pharmacy of Ukraine, Georgia https://orcid.org/0000-0003-3819-7331
Vira Kravchenko National University of Pharmacy of Ukraine, Georgia
Nino Abuladze Akaki Tsereteli State University , Georgia https://orcid.org/0000-0003-2189-7470
Ketevani Gabunia Akaki Tsereteli State University , Georgia https://orcid.org/0000-0002-5857-6593
Marina Giorgobiani Tbilisi State Medical University , Georgia https://orcid.org/0000-0003-0686-5227
Marika Sulashvili Tbilisi State Medical University , Georgia https://orcid.org/0000-0002-6338-4262

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Nodar Sulashvili, Margarita Beglaryan, Nana Gorgaslidze, Naira Chichoyan, Luiza Gabunia, Vira Kravchenko, Nato Alavidze, Tamar Tsintsadze, Igor Seniuk, Marina Giorgobiani (2024)

ПРОЯВЛЕНИЕ НАУЧНОГО ДИСКУРСА ПО КЛЮЧЕВЫМ АСПЕКТАМ ОЦЕНКИ ОСНОВНЫХ ФАКТОРОВ, ВЛИЯЮЩИХ НА ФОРМИРОВАНИЕ ПРОФЕССИОНАЛЬНОЙ ДЕЯТЕЛЬНОСТИ ФАРМАЦЕВТОВ В ГРУЗИИ В ЦЕЛОМ / THE MANIFESTATION OF SCIENTIFIC DISCOURSE OF KEY FIELD MATTER ASPECTS ON THE EVALUATION OF PRINCIPAL DETERMINANTS AFFECTING THE IMPACT OF PHARMACISTS' OCCUPATIONL FORMATION AND PHARMACISTS’ SOME VOCATIONAL SCOPE QUERIES IN GEORGIA IN GENERAL. Bulletin of the Medical Institute after Mehrabyan, 80.
10.53821/1829040X-2024.17-80

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Aim of the research was to study and analyze some issues of features of using of car-t cells in immunotherapy. The characterization of CAR-T cell products involves evaluating their phenotype, genotype, and functional attributes using techniques such as flow cytometry, PCR-based assays, and cytotoxicity assays. Long-term stability studies assess product viability, potency, and cytokine secretion profiles across different storage conditions to determine shelf-life and facilitate product logistics. Biomarkers serve as crucial tools in the field of cancer immunotherapy, aiding in patient selection and treatment optimization. In the context of chimeric antigen receptor (CAR) T cell therapy, biomarkers play a significant role in predicting treatment response, identifying potential toxicities, and guiding personalized treatment approaches. Predictive biomarkers in CAR-T cell therapy commonly center on the profiles of tumor antigen expression. The selection of target antigens plays a crucial role in treatment outcomes, with higher and more consistent expression levels correlating with better response rates. The tumor microenvironment (TME) significantly influences CAR-T cell activity. Biomarkers reflecting TME features, such as immune cell infiltration, cytokine profiles, and expression of inhibitory molecules, offer insights into the immunosuppressive nature of the TME and its effects on CAR-T cell effectiveness. Patients with an inflamed TME, marked by abundant effector T cells and low expression of inhibitory molecules like PD-L1, tend to respond better to CAR-T cell therapy. CAR-T cells demonstrate bystander killing effects, where nearby tumor cells without the target antigen are eradicated via a phenomenon called antigen spreading. This process is triggered by the release of cytokines and the presentation of tumor antigens by antigen-presenting cells (APCs), resulting in the activation of the body's own immune effector cells against the tumor cells. CAR-T cells exhibit strong antitumor capabilities, they can face resistance mechanisms within the tumor microenvironment. The immunosuppressive cell populations like regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), as well as inhibitory cytokines such as transforming growth factor-beta (TGF-β) and interleukin-10 (IL-10). The resistance mechanisms, strategies involve employing combination therapies with immune checkpoint inhibitors, cytokine modulators, and targeted therapies aimed at disrupting immunosuppressive pathways. CAR-T cell therapy has revolutionized cancer treatment by harnessing the power of the immune system to target and eliminate tumor cells.

Sulashvili, N., Davitashvili, M., Gorgaslidze, N., Gabunia, L., Beglaryan, M., Alavidze, N., … Sulashvili, M. (2024). THE SCIENTIFIC DISCUSSION OF SOME ISSUES OF FEATURES AND CHALLENGES OF USING OF CAR-T CELLS IN IMMUNOTHERAPY. Georgian Scientists, 6(4), 263–290. https://doi.org/10.52340/gs.2024.06.04.24

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Nodar Sulashvili, Tbilisi State Medical University

MD, PhD, Doctor of Theoretical Medicine In Pharmaceutical and Pharmacological Sciences, Invited Lecturer (Invited Professor) of Scientific Research-Skills Center at Tbilisi State Medical University; Professor of Division of Pharmacology of International School of Medicine at Alte University; Professor of Pharmacology of Faculty of Medicine at Georgian National University SEU; Associate Affiliated Professor of Medical Pharmacology of Faculty of Medicine at Sulkhan-Saba Orbeliani University; Associate Professor of Pharmacy Program at Shota Meskhia Zugdidi State University; Associate Professor of Medical Pharmacology at School of Medicine at David Aghmashenebeli University of Georgia; Associate Professor of Biochemistry and Pharmacology Direction at the University of Georgia, School of Health Sciences; Associate Professor of Pharmacology of Faculty of Medicine at East European University; Associate Professor of Pharmacology of Faculty of Dentistry and Pharmacy at Tbilisi Humanitarian Teaching University; Tbilisi, Georgia; Researcher of Department of Pharmaceutical Management of Yerevan State Medical University after Mkhitar Heratsi, Yerevan, Armenia

Magda Davitashvili, Iakob Gogebashvili Telavi State University

PhD, Doctor of Biological Sciences, Professor, Academician, Georgian Academy of Ecological Sciences, Program Coordinator of Quality Assurance Office at Iakob Gogebashvili Telavi State University (TeSaU), Telavi, Georgia.

Nana Gorgaslidze, Tbilisi State Medical University

MD, PhD, Doctor of Pharmaceutical Sciences, Professor of Tbilisi State Medical University, Head of The Department of Social and Clinical Pharmacy, Tbilisi, Georgia.

Luiza Gabunia

MD, PhD, Doctor of Medical Sciences, Professor, Director of the Scientific Research-Skills Center at Tbilisi State Medical University, Professor, Head of the Department of Clinical Pharmacology at Tbilisi State Medical University, Clinical Pharmacologist of The First University Clinic of Tbilisi State Medical University, Tbilisi, Georgia.

Margarita Beglaryan, Yerevan State Medical University

MD, PhD, Doctor of Pharmaceutical Sciences, Academician, Professor of Yerevan State Medical University, Head of the Department of Pharmaceutical Management, Yerevan, Armenia.

Nato Alavidze, East European University

MD, PhD, Doctor of Pharmaceutical Sciences, Professor of Akaki Tsereteli State University, Faculty of Medicine, Department of Pharmacy, Kutaisi, Georgia. Professor, Dean Faculty of Medicine at East European University, Tbilisi, Georgia.

Igor Seniuk, National University of Pharmacy of Ukraine

MD PhD, Doctor of Pharmaceutical Sciences, Dean of faculty of Pharmacy at National University of Pharmacy of Ukraine, Associate Professor of Biological Chemistry Department at National University of Pharmacy, Kharkiv, Ukraine.

Vira Kravchenko, National University of Pharmacy of Ukraine

MD, PhD, Doctor of Pharmaceutical Sciences, Academician, Professor, Head of The Biological Chemistry Department at National University of Pharmacy, Kharkiv, Ukraine.

Nino Abuladze, Akaki Tsereteli State University

MD, PhD, Doctor of Pharmaceutical Sciences, Professor of Akaki Tsereteli State University, Faculty of Medicine, Department of Pharmacy, Kutaisi, Georgia.

Ketevani Gabunia, Akaki Tsereteli State University

MD, PhD, Doctor of Pharmaceutical Sciences, Professor of Akaki Tsereteli State University, Faculty of Medicine, Department of Pharmacy, Kutaisi, Georgia.

Marina Giorgobiani, Tbilisi State Medical University

MD, PhD, Doctor of Medical Sciences, Professor of Tbilisi State Medical University, Department of Hygiene and Medical Ecology, Tbilisi, Georgia.

Marika Sulashvili, Tbilisi State Medical University

MD, Family Doctor, Invited Lecturer of Tbilisi State Medical University, Department of Molecular and Medical Genetics; Invited Professor of Molecular Biology, Medical Genetics and Medical Biochemistry at The University of Georgia, School of health Sciences, Tbilisi, Georgia.

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THE SCIENTIFIC DISCUSSION OF SOME ISSUES OF FEATURES AND CHALLENGES OF USING OF CAR-T CELLS IN IMMUNOTHERAPY

Authors

Nodar Sulashvili, Tbilisi State Medical University

Magda Davitashvili, Iakob Gogebashvili Telavi State University

Nana Gorgaslidze, Tbilisi State Medical University

Luiza Gabunia

Margarita Beglaryan, Yerevan State Medical University

Nato Alavidze, East European University

Igor Seniuk, National University of Pharmacy of Ukraine

Vira Kravchenko, National University of Pharmacy of Ukraine

Nino Abuladze, Akaki Tsereteli State University

Ketevani Gabunia, Akaki Tsereteli State University

Marina Giorgobiani, Tbilisi State Medical University

Marika Sulashvili, Tbilisi State Medical University

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